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Sample records for minimal photoautotroph non-coding

  1. Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942

    PubMed Central

    2011-01-01

    Background Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival. Results By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems. Conclusions Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell. PMID:21226929

  2. Non Coding RNA Molecules as Potential Biomarkers in Breast Cancer.

    PubMed

    De Leeneer, Kim; Claes, Kathleen

    2015-01-01

    The pursuit of minimally invasive biomarkers is a challenging but exciting area of research. Clearly, such markers would need to be sensitive and specific enough to aid in the detection of breast cancer at an early stage, would monitor progression of the disease, and could predict the individual patient's response to treatment. Unfortunately, to date, markers with such characteristics have not made it to the clinic for breast cancer. Past years, many studies indicated that the non-coding part of our genome (the so called 'junk' DNA), may be an ideal source for these biomarkers. In this chapter, the potential use of microRNAs and long non-coding RNAs as biomarkers will be discussed. PMID:26530371

  3. The non-coding RNAs as riboregulators

    PubMed Central

    Erdmann, Volker A.; Barciszewska, Miroslawa Z.; Szymanski, Maciej; Hochberg, Abraham; Groot, Nathan de; Barciszewski, Jan

    2001-01-01

    The non-coding RNAs database (http://biobases.ibch.poznan.pl/ncRNA/) contains currently available data on RNAs, which do not have long open reading frames and act as riboregulators. Non-coding RNAs are involved in the specific recognition of cellular nucleic acid targets through complementary base pairing to control cell growth and differentiation. Some of them are connected with several well known developmental and neuro­behavioral disorders. We have divided them into four groups. This paper is a short introduction to the database and presents its latest, updated edition. PMID:11125087

  4. Non-Coding RNAs in Transcriptional Regulation

    PubMed Central

    Chen, Yung-Chia Ariel; Aravin, Alexei A.

    2015-01-01

    Transcriptional gene silencing guided by small RNAs is a process conserved from protozoa to mammals. Small RNAs loaded into Argonaute family proteins direct repressive histone modifications or DNA cytosine methylation to homologous regions of the genome. Small RNA-mediated transcriptional silencing is required for many biological processes, including repression of transposable elements, maintaining the genome stability/integrity, and epigenetic inheritance of gene expression. Here we will summarize the current knowledge about small RNA biogenesis and mechanisms of transcriptional regulation in plants, Drosophila, C. elegans and mice. Furthermore, a rapidly growing number long non-coding RNAs (lncRNAs) have been implicated as important players in transcription regulation. We will discuss current models for long non-coding RNA-mediated gene regulation. PMID:26120554

  5. Non-coding RNAs in lung cancer

    PubMed Central

    Ricciuti, Biagio; Mecca, Carmen; Crinò, Lucio; Baglivo, Sara; Cenci, Matteo; Metro, Giulio

    2014-01-01

    The discovery that protein-coding genes represent less than 2% of all human genome, and the evidence that more than 90% of it is actively transcribed, changed the classical point of view of the central dogma of molecular biology, which was always based on the assumption that RNA functions mainly as an intermediate bridge between DNA sequences and protein synthesis machinery. Accumulating data indicates that non-coding RNAs are involved in different physiological processes, providing for the maintenance of cellular homeostasis. They are important regulators of gene expression, cellular differentiation, proliferation, migration, apoptosis, and stem cell maintenance. Alterations and disruptions of their expression or activity have increasingly been associated with pathological changes of cancer cells, this evidence and the prospect of using these molecules as diagnostic markers and therapeutic targets, make currently non-coding RNAs among the most relevant molecules in cancer research. In this paper we will provide an overview of non-coding RNA function and disruption in lung cancer biology, also focusing on their potential as diagnostic, prognostic and predictive biomarkers. PMID:25593996

  6. Biogeography of photoautotrophs in the high polar biome

    PubMed Central

    Pointing, Stephen B.; Burkhard Büdel; Convey, Peter; Gillman, Len N.; Körner, Christian; Leuzinger, Sebastian; Vincent, Warwick F.

    2015-01-01

    The global latitudinal gradient in biodiversity weakens in the high polar biome and so an alternative explanation for distribution of Arctic and Antarctic photoautotrophs is required. Here we identify how temporal, microclimate and evolutionary drivers of biogeography are important, rather than the macroclimate features that drive plant diversity patterns elsewhere. High polar ecosystems are biologically unique, with a more central role for bryophytes, lichens and microbial photoautotrophs over that of vascular plants. Constraints on vascular plants arise mainly due to stature and ontogenetic barriers. Conversely non-vascular plant and microbial photoautotroph distribution is correlated with favorable microclimates and the capacity for poikilohydric dormancy. Contemporary distribution also depends on evolutionary history, with adaptive and dispersal traits as well as legacy influencing biogeography. We highlight the relevance of these findings to predicting future impacts on diversity of polar photoautotrophs and to the current status of plants in Arctic and Antarctic conservation policy frameworks. PMID:26442009

  7. Non-coding genome functions in diabetes.

    PubMed

    Cebola, Inês; Pasquali, Lorenzo

    2016-01-01

    Most of the genetic variation associated with diabetes, through genome-wide association studies, does not reside in protein-coding regions, making the identification of functional variants and their eventual translation to the clinic challenging. In recent years, high-throughput sequencing-based methods have enabled genome-scale high-resolution epigenomic profiling in a variety of human tissues, allowing the exploration of the human genome outside of the well-studied coding regions. These experiments unmasked tens of thousands of regulatory elements across several cell types, including diabetes-relevant tissues, providing new insights into their mechanisms of gene regulation. Regulatory landscapes are highly dynamic and cell-type specific and, being sensitive to DNA sequence variation, can vary with individual genomes. The scientific community is now in place to exploit the regulatory maps of tissues central to diabetes etiology, such as pancreatic progenitors and adult islets. This giant leap forward in the understanding of pancreatic gene regulation is revolutionizing our capacity to discriminate between functional and non-functional non-coding variants, opening opportunities to uncover regulatory links between sequence variation and diabetes susceptibility. In this review, we focus on the non-coding regulatory landscape of the pancreatic endocrine cells and provide an overview of the recent developments in this field. PMID:26438568

  8. Microdroplet photobioreactor for the photoautotrophic culture of microalgal cells.

    PubMed

    Sung, Young Joon; Kim, Jaoon Young Hwan; Bong, Ki Wan; Sim, Sang Jun

    2016-02-01

    Microalgae, unicellular photoautotrophic microorganisms, have attracted great attention for the production of biofuel and high-value products, but the commercial use of microalgae has been limited by low photosynthetic productivity. To overcome this limitation, it is required to develop an efficient platform for the rapid evaluation of photoautotrophic growth performance and productivity of microalgal strains. Here we describe a droplet-based photobioreactor for high-throughput analysis of the photoautotrophic growth of microalgal cells. By integrating micropillar arrays and adjusting the height of the microchamber, we could accurately monitor the growth kinetics of microalgae in an immobilized microdroplet and improve the transfer rate of CO2 into the microdroplet photobioreactor with an increased contact area between the microdroplet and PDMS surface. The improvement of CO2 transfer into the microdroplet was also confirmed by improved microalgal cell growth and a decrease in pH measured using colorimetric and fluorescence-based assays. The photoautotrophic growth kinetics of Chlorella vulgaris were measured under different CO2 concentrations (ambient, 1%, 2.5%, 5% and 7.5%) and light intensity (35, 55, 100, 150, and 200 μmol photons per m(2) per s) conditions, which are key factors for photoautotrophic growth. Chlorella vulgaris in a microdroplet showed better cell growth performance compared to a flask culture due to the reduced shading effects and improved mass transfer. Finally, we could evaluate the photoautotrophic growth performance of four microalgal strains (Chlorella vulgaris, Chlorella protothecoides, Chlorella sorokiniana and Neochloris oleoabundans) for 120 hours. These results demonstrate that our microdroplet system can be used as an efficient photobioreactor for the rapid evaluation of the photoautotrophic growth of microalgal strains under various conditions. PMID:26673975

  9. Fluorescence characteristics of photoautotrophic soybean cells.

    PubMed

    Xu, C; Rogers, S M; Goldstein, C; Widholm, J M; Govindjee

    1989-08-01

    We report here the first measurements on chlorophyll (Chl) a fluorescence characteristics of photoautotrophic soybean cells (cell lines SB-P and SBI-P). The cell fluorescence is free from severe distortion problems encountered in higher plant leaves. Chl a fluorescence spectra at 77 K show, after correction for the spectral sensitivity of the photomultiplier and the emission monochromator, peaks at 688, 696 and 745 nm, representing antenna systems of photosystem II-CP43 and CP47, and photosystem I, respectively. Calculations, based on the complementary area over the Chl a fluorescence induction curve, indicated a ratio of 6 of the mobile plastoquinone (including QB) to the primary stable electron acceptor, the bound plastoquinone QA. A ratio of one between the secondary stable electron acceptor, bound plastoquinone QB, and its reduced form QB (-) was obtained by using a double flash technique. Owing to this ratio, the flash number dependence of the Chl a fluorescence showed a distinct period of four, implying a close relationship to the 'S' state of the oxygen evolution mechanism. Analysis of the QA (-) reoxidation kinetics showed (1) the halftime of each of the major decay components (∼ 300 μs fast and ∼ 30 ms slow) increases with the increase of diuron and atrazine concentrations; and (2) the amplitudes of the fast and the slow components change in a complementary fashion, the fast component disappearing at high concentrations of the inhibitors. This implies that the inhibitors used are able to totally displace QB. In intact soybean cells, the relative amplitude of the 30 ms to 300 μs component is higher (40:60) than that in spinach chloroplasts (30:70), implying a larger contribution of the centers with unbound QB. SB-P and SBI-P soybean cells display a slightly different sensitivity of QA (-) decay to inhibitors. PMID:24424528

  10. Non-coding landscapes of colorectal cancer

    PubMed Central

    Ragusa, Marco; Barbagallo, Cristina; Statello, Luisa; Condorelli, Angelo Giuseppe; Battaglia, Rosalia; Tamburello, Lucia; Barbagallo, Davide; Di Pietro, Cinzia; Purrello, Michele

    2015-01-01

    For two decades Vogelstein’s model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy. PMID:26556998

  11. Non-coding RNAs and atherosclerosis

    PubMed Central

    Fernández-Hernando, Carlos

    2014-01-01

    Non-coding RNAs (ncRNAs) represent a class of RNA molecules that typically do not code for proteins. Emerging data suggest that ncRNAs play an important role in several physiological and pathological conditions such as cancer and cardiovascular diseases (CVDs) including atherosclerosis. The best-characterized ncRNAs are the microRNAs (miRNAs), which are small, ~22 nucleotide (nt) sequences of RNA that regulate gene expression at the posttranscriptional level through transcript degradation or translational repression. MiRNAs control several aspects of atherosclerosis including endothelial cell, vascular smooth cell, and macrophage functions as well as lipoprotein metabolism. Apart from miRNAs, recently ncRNAs, especially long ncRNAs (lncRNAs), have emerged as important potential regulators of the progression of atherosclerosis. However, the molecular mechanism of their regulation and function as well as significance of other ncRNAs such as small nucleolar RNAs (snoRNAs) during atherogenesis is largely unknown. In this review, we summarize the recent findings in the field, highlighting the importance of ncRNAs in atherosclerosis and discuss their potential use as therapeutic targets in CVDs. PMID:24623179

  12. Non coding RNAs in aortic aneurysmal disease.

    PubMed

    Duggirala, Aparna; Delogu, Francesca; Angelini, Timothy G; Smith, Tanya; Caputo, Massimo; Rajakaruna, Cha; Emanueli, Costanza

    2015-01-01

    An aneurysm is a local dilatation of a vessel wall which is >50% its original diameter. Within the spectrum of cardiovascular diseases, aortic aneurysms are among the most challenging to treat. Most patients present acutely after aneurysm rupture or dissection from a previous asymptomatic condition and are managed by open surgical or endovascular repair. In addition, patients may harbor concurrent disease contraindicating surgical intervention. Collectively, these factors have driven the search for alternative methods of identifying, monitoring and treating aortic aneurisms using less invasive approaches. Non-coding RNA (ncRNAs) are emerging as new fundamental regulators of gene expression. The small microRNAs have opened the field of ncRNAs capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers for aortic aneurysm. More recently, long ncRNAs (lncRNAs) have started to be actively investigated, leading to first exciting reports, which further suggest their important and yet largely unexplored contribution to vascular physiology and disease. This review introduces the different ncRNA types and focus at ncRNA roles in aorta aneurysms. We discuss the potential of therapeutic interventions targeting ncRNAs and we describe the research models allowing for mechanistic studies and clinical translation attempts for controlling aneurysm progression. Furthermore, we discuss the potential role of microRNAs and lncRNAs as clinical biomarkers. PMID:25883602

  13. Non coding RNAs in aortic aneurysmal disease

    PubMed Central

    Duggirala, Aparna; Delogu, Francesca; Angelini, Timothy G.; Smith, Tanya; Caputo, Massimo; Rajakaruna, Cha; Emanueli, Costanza

    2015-01-01

    An aneurysm is a local dilatation of a vessel wall which is >50% its original diameter. Within the spectrum of cardiovascular diseases, aortic aneurysms are among the most challenging to treat. Most patients present acutely after aneurysm rupture or dissection from a previous asymptomatic condition and are managed by open surgical or endovascular repair. In addition, patients may harbor concurrent disease contraindicating surgical intervention. Collectively, these factors have driven the search for alternative methods of identifying, monitoring and treating aortic aneurisms using less invasive approaches. Non-coding RNA (ncRNAs) are emerging as new fundamental regulators of gene expression. The small microRNAs have opened the field of ncRNAs capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers for aortic aneurysm. More recently, long ncRNAs (lncRNAs) have started to be actively investigated, leading to first exciting reports, which further suggest their important and yet largely unexplored contribution to vascular physiology and disease. This review introduces the different ncRNA types and focus at ncRNA roles in aorta aneurysms. We discuss the potential of therapeutic interventions targeting ncRNAs and we describe the research models allowing for mechanistic studies and clinical translation attempts for controlling aneurysm progression. Furthermore, we discuss the potential role of microRNAs and lncRNAs as clinical biomarkers. PMID:25883602

  14. Non-coding RNA repertoires in malignant pleural mesothelioma.

    PubMed

    Quinn, Leah; Finn, Stephen P; Cuffe, Sinead; Gray, Steven G

    2015-12-01

    Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. There are limited treatment options, with no second line standard of care for those who fail first line chemotherapy. Recent advances have been made to characterise the underlying molecular mechanisms of mesothelioma, in the hope of providing new targets for therapy. With the discovery that non-coding regions of our DNA are more than mere junk, the field of research into non-coding RNAs (ncRNAs) has exploded in recent years. Non-coding RNAs have diverse and important roles in a variety of cellular processes, but are also implicated in malignancy. In the following review, we discuss two types of non-coding RNAs, long non-coding RNAs and microRNAs, in terms of their role in the pathogenesis of MPM and their potential as both biomarkers and as therapeutic targets in this disease. PMID:26791801

  15. Non-coding RNAs in epithelial immunity to Cryptosporidium infection

    PubMed Central

    Zhou, Rui; Feng, Yaoyu; Chen, Xian-Ming

    2015-01-01

    SUMMARY Cryptosporidium spp. is a protozoan parasite that infects the gastrointestinal epithelium and causes diarrhoeal disease worldwide. It is one of the most common pathogens responsible for moderate to severe diarrhoea in children younger than 2 years. Because of the ‘minimally invasive’ nature of Cryptosporidium infection, mucosal epithelial cells are critical to the host’s anti-Cryptosporidium immunity. Gastrointestinal epithelial cells not only provide the first and most rapid defence against Cryptosporidium infection, they also mobilize immune effector cells to the infection site to activate adaptive immunity. Recent advances in genomic research have revealed the existence of a large number of non-protein-coding RNA transcripts, so called non-coding RNAs (ncRNAs), in mammalian cells. Some ncRNAs may be key regulators for diverse biological functions, including innate immune responses. Specifically, ncRNAs may modulate epithelial immune responses at every step of the innate immune network following Cryptosporidium infection, including production of antimicrobial molecules, expression of cytokines/chemokines, release of epithelial cell-derived exosomes, and feedback regulation of immune homoeostasis. This review briefly summarizes the current science on ncRNA regulation of innate immunity to Cryptosporidium, with a focus on microRNA-associated epithelial immune responses. PMID:24828969

  16. Mapping photoautotrophic metabolism with isotopically nonstationary (13)C flux analysis.

    PubMed

    Young, Jamey D; Shastri, Avantika A; Stephanopoulos, Gregory; Morgan, John A

    2011-11-01

    Understanding in vivo regulation of photoautotrophic metabolism is important for identifying strategies to improve photosynthetic efficiency or re-route carbon fluxes to desirable end products. We have developed an approach to reconstruct comprehensive flux maps of photoautotrophic metabolism by computational analysis of dynamic isotope labeling measurements and have applied it to determine metabolic pathway fluxes in the cyanobacterium Synechocystis sp. PCC6803. Comparison to a theoretically predicted flux map revealed inefficiencies in photosynthesis due to oxidative pentose phosphate pathway and malic enzyme activity, despite negligible photorespiration. This approach has potential to fill important gaps in our understanding of how carbon and energy flows are systemically regulated in cyanobacteria, plants, and algae. PMID:21907300

  17. Disruption of photoautotrophic intertidal mats by filamentous fungi.

    PubMed

    Carreira, Cátia; Staal, Marc; Falkoski, Daniel; de Vries, Ronald P; Middelboe, Mathias; Brussaard, Corina P D

    2015-08-01

    Ring-like structures, 2.0-4.8 cm in diameter, observed in photosynthetic microbial mats on the Wadden Sea island Schiermonnikoog (the Netherlands) showed to be the result of the fungus Emericellopsis sp. degrading the photoautotrophic top layer of the mat. The mats were predominantly composed of cyanobacteria and diatoms, with large densities of bacteria and viruses both in the top photosynthetic layer and in the underlying sediment. The fungal attack cleared the photosynthetic layer; however, no significant effect of the fungal lysis on the bacterial and viral abundances could be detected. Fungal-mediated degradation of the major photoautotrophs could be reproduced by inoculation of non-infected mat with isolated Emericellopsis sp., and with an infected ring sector. Diatoms were the first re-colonizers followed closely by cyanobacteria that after about 5 days dominated the space. The study demonstrated that the fungus Emericellopsis sp. efficiently degraded a photoautotrophic microbial mat, with potential implications for mat community composition, spatial structure and productivity. PMID:25728280

  18. Towards structural classification of long non-coding RNAs.

    PubMed

    Sanbonmatsu, Karissa Y

    2016-01-01

    While long non-coding RNAs play key roles in disease and development, few structural studies have been performed to date for this emerging class of RNAs. Previous structural studies are reviewed, and a pipeline is presented to determine secondary structures of long non-coding RNAs. Similar to riboswitches, experimentally determined secondary structures of long non-coding RNAs for one species, may be used to improve sequence/structure alignments for other species. As riboswitches have been classified according to their secondary structure, a similar scheme could be used to classify long non-coding RNAs. This article is part of a Special Issue titled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID:26537437

  19. Circulating Non-coding RNA as Biomarkers in Colorectal Cancer.

    PubMed

    Ferracin, Manuela; Lupini, Laura; Mangolini, Alessandra; Negrini, Massimo

    2016-01-01

    Recent studies suggested that colorectal cancer influences the types and quantity of nucleic acids - especially microRNAs - detected in the bloodstream. Concentration of circulating (cell-free) microRNAs, and possibly of other non-coding RNAs, could therefore serve as valuable colorectal cancer biomarker and could deliver insight into the disease process. This chapter addresses the recent discoveries on circulating microRNA and long non-coding RNA as diagnostic or prognostic biomarkers in colorectal cancer. PMID:27573900

  20. Functional roles of non-coding Y RNAs

    PubMed Central

    Kowalski, Madzia P.; Krude, Torsten

    2015-01-01

    Non-coding RNAs are involved in a multitude of cellular processes but the biochemical function of many small non-coding RNAs remains unclear. The family of small non-coding Y RNAs is conserved in vertebrates and related RNAs are present in some prokaryotic species. Y RNAs are also homologous to the newly identified family of non-coding stem-bulge RNAs (sbRNAs) in nematodes, for which potential physiological functions are only now emerging. Y RNAs are essential for the initiation of chromosomal DNA replication in vertebrates and, when bound to the Ro60 protein, they are involved in RNA stability and cellular responses to stress in several eukaryotic and prokaryotic species. Additionally, short fragments of Y RNAs have recently been identified as abundant components in the blood and tissues of humans and other mammals, with potential diagnostic value. While the number of functional roles of Y RNAs is growing, it is becoming increasingly clear that the conserved structural domains of Y RNAs are essential for distinct cellular functions. Here, we review the biochemical functions associated with these structural RNA domains, as well as the functional conservation of Y RNAs in different species. The existing biochemical and structural evidence supports a domain model for these small non-coding RNAs that has direct implications for the modular evolution of functional non-coding RNAs. PMID:26159929

  1. Long non-coding RNA PVT1 and cancer.

    PubMed

    Cui, Ming; You, Lei; Ren, Xiaoxia; Zhao, Wenjing; Liao, Quan; Zhao, Yupei

    2016-02-26

    Genome-wide sequencing technologies have led to the identification of many non-coding RNAs and revealed an important role for these molecules in cancer. Although there have been many studies on the role of short non-coding RNAs in cancer, much work remains to characterize the functions of long non-coding RNAs. PVT1, a long non-coding RNA encoded by the human PVT1 gene, is located in the well-known cancer-related region 8q24, also known as the 8q24 'gene desert.' PVT1 has three main molecular mechanisms of action: participating in DNA rearrangements, encoding microRNAs, and interacting with MYC. Studies on the association between PVT1 and cancer have shown that PVT1 is a potential oncogene in a variety of cancer types. However, the underlying molecular mechanisms of PVT1 in cancer remain unknown. Further studies of PVT1 will be required to test the utility of this molecule as a target for cancer diagnosis and therapy, and they should also increase our understanding of the role of long non-coding RNAs in tumorigenesis. PMID:26850852

  2. Non-coding RNAs in Mammary Gland Development and Disease.

    PubMed

    Sandhu, Gurveen K; Milevskiy, Michael J G; Wilson, Wesley; Shewan, Annette M; Brown, Melissa A

    2016-01-01

    Non-coding RNAs (ncRNAs) are untranslated RNA molecules that function to regulate the expression of numerous genes and associated biochemical pathways and cellular functions. NcRNAs include small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs). They participate in the regulation of all developmental processes and are frequently aberrantly expressed or functionally defective in disease. This Chapter will focus on the role of ncRNAs, in particular miRNAs and lncRNAs, in mammary gland development and disease. PMID:26659490

  3. Non-coding RNA in neural function, disease, and aging

    PubMed Central

    Szafranski, Kirk; Abraham, Karan J.; Mekhail, Karim

    2015-01-01

    Declining brain and neurobiological function is arguably one of the most common features of human aging. The study of conserved aging processes as well as the characterization of various neurodegenerative diseases using different genetic models such as yeast, fly, mouse, and human systems is uncovering links to non-coding RNAs. These links implicate a variety of RNA-regulatory processes, including microRNA function, paraspeckle formation, RNA–DNA hybrid regulation, nucleolar RNAs and toxic RNA clearance, amongst others. Here we highlight these connections and reveal over-arching themes or questions related to recently appreciated roles of non-coding RNA in neural function and dysfunction across lifespan. PMID:25806046

  4. Photoautotrophic microorganisms as a carbon source for temperate soil invertebrates.

    PubMed

    Schmidt, Olaf; Dyckmans, Jens; Schrader, Stefan

    2016-01-01

    We tested experimentally if photoautotrophic microorganisms are a carbon source for invertebrates in temperate soils. We exposed forest or arable soils to a (13)CO2-enriched atmosphere and quantified (13)C assimilation by three common animal groups: earthworms (Oligochaeta), springtails (Hexapoda) and slugs (Gastropoda). Endogeic earthworms (Allolobophora chlorotica) and hemiedaphic springtails (Ceratophysella denticulata) were highly (13)C enriched when incubated under light, deriving up to 3.0 and 17.0%, respectively, of their body carbon from the microbial source in 7 days. Earthworms assimilated more (13)C in undisturbed soil than when the microbial material was mixed into the soil, presumably reflecting selective surface grazing. By contrast, neither adult nor newly hatched terrestrial slugs (Deroceras reticulatum) grazed on algal mats. Non-photosynthetic (13)CO2 fixation in the dark was negligible. We conclude from these preliminary laboratory experiments that, in addition to litter and root-derived carbon from vascular plants, photoautotrophic soil surface microorganisms (cyanobacteria, algae) may be an ecologically important carbon input route for temperate soil animals that are traditionally assigned to the decomposer channel in soil food web models and carbon cycling studies. PMID:26740559

  5. Non-coding RNAs in cancer brain metastasis.

    PubMed

    Wu, Kerui; Sharma, Sambad; Venkat, Suresh; Liu, Keqin; Zhou, Xiaobo; Watabe, Kounosuke

    2016-01-01

    More than 90% of cancer death is attributed to metastatic disease, and the brain is one of the major metastatic sites of melanoma, colon, renal, lung and breast cancers. Despite the recent advancement of targeted therapy for cancer, the incidence of brain metastasis is increasing. One reason is that most therapeutic drugs can't penetrate blood-brain-barrier and tumor cells find the brain as sanctuary site. In this review, we describe the pathophysiology of brain metastases to introduce the latest understandings of metastatic brain malignancies. This review also particularly focuses on non-coding RNAs and their roles in cancer brain metastasis. Furthermore, we discuss the roles of the extracellular vesicles as they are known to transport information between cells to initiate cancer cell-microenvironment communication. The potential clinical translation of non-coding RNAs as a tool for diagnosis and for treatment is also discussed in this review. At the end, the computational aspects of non-coding RNA detection, the sequence and structure calculation and epigenetic regulation of non-coding RNA in brain metastasis are discussed. PMID:26709907

  6. The tumour hypoxia induced non-coding transcriptome.

    PubMed

    Choudhry, Hani; Harris, Adrian L; McIntyre, Alan

    2016-01-01

    Recent investigations have highlighted the importance of the non-coding genome in regions of hypoxia in tumours. Such regions are frequently found in solid tumours, and are associated with worse patient survival and therapy resistance. Hypoxia stabilises the transcription factors, hypoxia inducible factors (HIF1α and HIF2α) which coordinate transcriptomic changes that occur in hypoxia. The changes in gene expression induced by HIF1α and HIF2α contribute to many of the hallmarks of cancer phenotypes and enable tumour growth, survival and invasion in the hypoxic tumour microenvironment. Non-coding RNAs, in particular microRNAs (miRNAs), which regulate mRNA stability and translation, and long-non-coding RNAs (lncRNAs), which have diverse functions including chromatin modification and transcriptional regulation, are also important in enabling the key hypoxia regulated processes. They have roles in the regulation of metabolism, angiogenesis, autophagy, invasion and metastasis in the hypoxic microenvironment. Furthermore, HIF1α and HIF2α expression and stabilisation are also regulated by both miRNAs and lncRNAs. Here we review the recent developments in the expression, regulation and functions of miRNAs, lncRNAs and other non-coding RNA classes in tumour hypoxia. PMID:26806607

  7. Beyond the proteome: non-coding regulatory RNAs

    PubMed Central

    Szymański, Maciej; Barciszewski, Jan

    2002-01-01

    A variety of RNA molecules have been found over the last 20 years to have a remarkable range of functions beyond the well-known roles of messenger, ribosomal and transfer RNAs. Here, we present a general categorization of all non-coding RNAs and briefly discuss the ones that affect transcription, translation and protein function. PMID:12049667

  8. Uncovering RNA Editing Sites in Long Non-Coding RNAs

    PubMed Central

    Picardi, Ernesto; D’Erchia, Anna Maria; Gallo, Angela; Montalvo, Antonio; Pesole, Graziano

    2014-01-01

    RNA editing is an important co/post-transcriptional molecular process able to modify RNAs by nucleotide insertions/deletions or substitutions. In human, the most common RNA editing event involves the deamination of adenosine (A) into inosine (I) through the adenosine deaminase acting on RNA proteins. Although A-to-I editing can occur in both coding and non-coding RNAs, recent findings, based on RNA-seq experiments, have clearly demonstrated that a large fraction of RNA editing events alter non-coding RNAs sequences including untranslated regions of mRNAs, introns, long non-coding RNAs (lncRNAs), and low molecular weight RNAs (tRNA, miRNAs, and others). An accurate detection of A-to-I events occurring in non-coding RNAs is of utmost importance to clarify yet unknown functional roles of RNA editing in the context of gene expression regulation and maintenance of cell homeostasis. In the last few years, massive transcriptome sequencing has been employed to identify putative RNA editing changes at genome scale. Despite several efforts, the computational prediction of A-to-I sites in complete eukaryotic genomes is yet a challenging task. We have recently developed a software package, called REDItools, in order to simplify the detection of RNA editing events from deep sequencing data. In the present work, we show the potential of our tools in recovering A-to-I candidates from RNA-Seq experiments as well as guidelines to improve the RNA editing detection in non-coding RNAs, with specific attention to the lncRNAs. PMID:25538940

  9. Photoautotrophic Growth of Soybean Cells in Suspension Culture

    PubMed Central

    Horn, Michael E.; Sherrard, Joseph H.; Widholm, Jack M.

    1983-01-01

    Highly chlorophyllous photomixotrophic callus was visually selected from callus originating from soybean (Glycine max (L.) Merr. var. Corsoy) cotyledon. Suspension cultures initiated from this callus became photoautotrophic under continuous light with an atmosphere of 5% CO2 (balance air). Dry weight increases of 1000 to 1400% in the 2-week subculture period have been observed. The cellular Chl content ranged from 4.4 to 5.9 micrograms per milligram dry weight which is about 75 to 90% of the Chl content in soybean leaves under equivalent illumination (300 micro-Einsteins per square meter per second). No growth can be observed in the dark in sucrose-lacking medium or in the presence of 0.5 micromolar 3-(3,4-dichlorophenyl)-1,1-dimethylurea, a concentration which does not inhibit heterotrophic growth (on sucrose). Photoautotrophic growth has an absolute requirement for elevated CO2 concentrations (>1%). During the 14-day subculture period, growth (fresh weight and dry weight) is logarithmic. Photosynthesis quickly increases after day 4, reaching a peak of 83 micromoles CO2 incorporated per milligram Chl per hour while dark respiration decreases 90% from day 2 to day 6. The pH of the growth medium quickly drops from 7.0 to 4.5 before slowly increasing to 5.0 by day 14. At this pH range and light intensity (200-300 microEinsteins per square meter per second), no O2 evolution could be detected although at high pH and light intensity O2 evolution was recorded. PMID:16663019

  10. Long non-coding RNAs and hepatocellular carcinoma

    PubMed Central

    YU, FU-JUN; ZHENG, JIAN-JIAN; DONG, PEI-HONG; FAN, XIAO-MING

    2015-01-01

    Recent advances in next-generation sequencing technology in transcriptome analysis have helped identify numerous non-coding RNAs. The long non-coding RNA (lncRNA) is commonly defined as an RNA molecule with a length of 200 bp-100 kbp that lacks protein-coding potential. LncRNAs play a critical role in the regulation of gene expression, including chromatin modification, transcription and post-transcriptional processing. It has been confirmed that dysregulation of lncRNAs is associated with a number of human diseases, particularly tumors. In this study, we focused on the most extensively investigated lncRNAs in hepatocellular carcinoma (HCC). The biological functions and molecular mechanisms of the majority of lncRNAs have yet to be investigated. The improved knowledge on lncRNAs in HCC may help identify lncRNAs that may be used as novel prognostic markers and therapeutic targets. PMID:25469263

  11. Dysregulation of non-coding RNAs in gastric cancer

    PubMed Central

    Yang, Qing; Zhang, Ren-Wen; Sui, Peng-Cheng; He, Hai-Tao; Ding, Lei

    2015-01-01

    Gastric cancer (GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs (ncRNAs), primarily microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of non-coding RNAs, especially miRNAs and lncRNAs, in GC. We summarize instances of aberrant expression of the ncRNAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how ncRNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncRNAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncRNAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncRNAs have been identified as targets for the treatment of GC. PMID:26494954

  12. Functional annotation of non-coding sequence variants

    PubMed Central

    Ritchie, Graham R. S.; Dunham, Ian; Zeggini, Eleftheria; Flicek, Paul

    2016-01-01

    Identifying functionally relevant variants against the background of ubiquitous genetic variation is a major challenge in human genetics. For variants that fall in protein-coding regions our understanding of the genetic code and splicing allow us to identify likely candidates, but interpreting variants that fall outside of genic regions is more difficult. Here we present a new tool, GWAVA, which supports prioritisation of non-coding variants by integrating a range of annotations. PMID:24487584

  13. Transcription control by long non-coding RNAs

    PubMed Central

    Faust, Tyler

    2012-01-01

    Non-coding RNAs have been found to regulate many cellular processes and thus expand the functional genetic repertoire contained within the genome. With the recent advent of genomic tools, it is now evident that these RNA molecules play central regulatory roles in many transcriptional programs. Here we discuss how they are targeted to promoters in several cases and how they operate at specific points in the transcription cycle to precisely control gene expression. PMID:22414755

  14. The Landscape of long non-coding RNA classification

    PubMed Central

    St Laurent, Georges; Wahlestedt, Claes; Kapranov, Philipp

    2015-01-01

    Advances in the depth and quality of transcriptome sequencing have revealed many new classes of long non-coding RNAs (lncRNAs). lncRNA classification has mushroomed to accommodate these new findings, even though the real dimensions and complexity of the non-coding transcriptome remain unknown. Although evidence of functionality of specific lncRNAs continues to accumulate, conflicting, confusing, and overlapping terminology has fostered ambiguity and lack of clarity in the field in general. The lack of fundamental conceptual un-ambiguous classification framework results in a number of challenges in the annotation and interpretation of non-coding transcriptome data. It also might undermine integration of the new genomic methods and datasets in an effort to unravel function of lncRNA. Here, we review existing lncRNA classifications, nomenclature, and terminology. Then we describe the conceptual guidelines that have emerged for their classification and functional annotation based on expanding and more comprehensive use of large systems biology-based datasets. PMID:25869999

  15. Incorporating Non-Coding Annotations into Rare Variant Analysis

    PubMed Central

    Richardson, Tom G.; Campbell, Colin; Timpson, Nicholas J; Gaunt, Tom R.

    2016-01-01

    Background The success of collapsing methods which investigate the combined effect of rare variants on complex traits has so far been limited. The manner in which variants within a gene are selected prior to analysis has a crucial impact on this success, which has resulted in analyses conventionally filtering variants according to their consequence. This study investigates whether an alternative approach to filtering, using annotations from recently developed bioinformatics tools, can aid these types of analyses in comparison to conventional approaches. Methods & Results We conducted a candidate gene analysis using the UK10K sequence and lipids data, filtering according to functional annotations using the resource CADD (Combined Annotation-Dependent Depletion) and contrasting results with ‘nonsynonymous’ and ‘loss of function’ consequence analyses. Using CADD allowed the inclusion of potentially deleterious intronic variants, which was not possible when filtering by consequence. Overall, different filtering approaches provided similar evidence of association, although filtering according to CADD identified evidence of association between ANGPTL4 and High Density Lipoproteins (P = 0.02, N = 3,210) which was not observed in the other analyses. We also undertook genome-wide analyses to determine how filtering in this manner compared to conventional approaches for gene regions. Results suggested that filtering by annotations according to CADD, as well as other tools known as FATHMM-MKL and DANN, identified association signals not detected when filtering by variant consequence and vice versa. Conclusion Incorporating variant annotations from non-coding bioinformatics tools should prove to be a valuable asset for rare variant analyses in the future. Filtering by variant consequence is only possible in coding regions of the genome, whereas utilising non-coding bioinformatics annotations provides an opportunity to discover unknown causal variants in non-coding

  16. Dynamic energy budgets in syntrophic symbiotic relationships between heterotrophic hosts and photoautotrophic symbionts.

    PubMed

    Muller, Erik B; Kooijman, Sebastiaan A L M; Edmunds, Peter J; Doyle, Francis J; Nisbet, Roger M

    2009-07-01

    In this paper we develop and investigate a dynamic energy budget (DEB) model describing the syntrophic symbiotic relationship between a heterotrophic host and an internal photoautotrophic symbiont. The model specifies the flows of matter and energy among host, symbiont and environment with minimal complexity and uses the concept of synthesizing units to describe smoothly the assimilation of multiple limiting factors, in particular inorganic carbon and nitrogen, and irradiance. The model has two passive regulation mechanisms: the symbiont shares only photosynthate that it cannot use itself, and the host delivers only excess nutrients to the symbiont. With parameter values plausible for scleractinian corals, we show that these two regulation mechanisms suffice to obtain a stable symbiotic relationship under constant ambient conditions, provided those conditions support sustenance of host and symbiont. Furthermore, the symbiont density in the host varies relatively little as a function of ambient food density, inorganic nitrogen and irradiance. This symbiont density tends to increase with light deprivation or nitrogen enrichment, either directly or via food. We also investigate the relative benefit each partner derives from the relationship and conclude that this relationship may shift from mutualism to parasitism as environmental conditions change. PMID:19285512

  17. Non-Coding RNAs in Primary Liver Cancer

    PubMed Central

    Ghidini, Michele; Braconi, Chiara

    2015-01-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with poor prognosis and limited therapeutic options. Over the past few years, many studies have evaluated the role of non-coding RNAs (ncRNAs) in hepatocarcinogenesis and tumor progression. ncRNAs were shown to have diagnostic, prognostic, and therapeutic potential in HCC. In this manuscript, we review the latest major discoveries concerning microRNAs and long ncRNAs in HCC pathogenesis, and discuss the potentials and the limitations for their use in clinical practice. PMID:26131450

  18. Non-Coding RNAs in Primary Liver Cancer.

    PubMed

    Ghidini, Michele; Braconi, Chiara

    2015-01-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with poor prognosis and limited therapeutic options. Over the past few years, many studies have evaluated the role of non-coding RNAs (ncRNAs) in hepatocarcinogenesis and tumor progression. ncRNAs were shown to have diagnostic, prognostic, and therapeutic potential in HCC. In this manuscript, we review the latest major discoveries concerning microRNAs and long ncRNAs in HCC pathogenesis, and discuss the potentials and the limitations for their use in clinical practice. PMID:26131450

  19. A photoautotrophic source for lycopane in marine water columns

    NASA Technical Reports Server (NTRS)

    Wakeham, Stuart G.; Freeman, Katherine H.; Pease, Tamara K.; Hayes, J. M.

    1993-01-01

    Suspended particulate matter and recent sediments from diverse oceanic sites have been investigated for their contents of lycopane. Lycopane was present in all samples, including both oxic and anoxic water column and sediments. The highest concentrations in the water column were found in surface waters of the central Pacific gyre (1.5 ng/L) and in the anoxic waters of the Cariaco Trench (1.1 ng/L) and the Black Sea (0.3 ng/L). Vertical concentration profiles suggest that lycopane is probably algal in origin. Moreover, biogeochemical conditions in anoxic zones apparently result in a secondary production of lycopane from an as yet unidentified precursor. Compound-specific carbon isotopic analyses have been carried out on lycopane from water column and sediment samples. Isotopic compositions of lycopane range between -23.6 and -32.9 percent and are consistent with a photoautotrophic origin. We postulate that some lycopane is produced in surface waters of the ocean, while additional lycopane is produced in anoxic zones by anaerobic microbial action on an algal precursor.

  20. Biotransformations of monoterpenes by photoautotrophic micro-organisms.

    PubMed

    Balcerzak, L; Lipok, J; Strub, D; Lochyński, S

    2014-12-01

    Monoterpenes are widely used in food technology, cosmetic and pharmaceutical industries and as compounds of agricultural importance. It is known that compounds comprising this class can be transformed by a variety of organisms, namely by: bacteria, fungi, yeasts, plants or isolated enzymes. Biotransformations, as one of the most important tools of green chemistry, allow obtaining new products using whole cells of micro-organisms or isolated enzymes in mild reaction conditions. Therefore, biotransformations of monoterpenes, by different type of reaction such as: epoxidation, oxidation and stereoselective hydroxylation, resulted in the production of so desired, enantiomerically defined compounds that can be advised as natural seem to be interesting. Bearing in mind that such processes are carried out also by easy to maintain, photoautotrophic micro-organisms cultivated at large scale, this paper is focused on biotransformations of acyclic, monocyclic and bicyclic monoterpenes by freshwater or haliphylic cyanobacteria and microalgae on the way of mainly stereoselective hydroxylation. Moreover, aspects of potential industrial application of obtained products in medicine, perfume, cosmetics and food industry are discussed. PMID:25175902

  1. Main photoautotrophic components of biofilms in natural draft cooling towers.

    PubMed

    Hauer, Tomáš; Čapek, Petr; Böhmová, Petra

    2016-05-01

    While photoautotrophic organisms are an important component of biofilms that live in certain regions of natural draft cooling towers, little is known about these communities. We therefore examined 18 towers at nine sites to identify the general patterns of community assembly in three distinct tower parts, and we examined how community structures differ depending on geography. We also compared the newly acquired data with previously published data. The bottom sections of draft cooling towers are mainly settled by large filamentous algae, primarily Cladophora glomerata. The central portions of towers host a small amount of planktic algae biomass originating in the cooling water. The upper fourths of towers are colonized by biofilms primarily dominated by cyanobacteria, e.g., members of the genera Gloeocapsa and Scytonema. A total of 41 taxa of phototrophic microorganisms were identified. Species composition of the upper fourth of all towers was significantly affected by cardinal position. There was different species composition at positions facing north compared to positions facing south. West- and east-facing positions were transitory and highly similar to each other in terms of species composition. Biofilms contribute to the degradation of paint coatings inside towers. PMID:26508444

  2. Viroids, infectious long non-coding RNAs with autonomous replication.

    PubMed

    Gago-Zachert, Selma

    2016-01-01

    Transcriptome deep-sequencing studies performed during the last years confirmed that the vast majority of the RNAs transcribed in higher organisms correspond to several types of non-coding RNAs including long non-coding RNAs (lncRNAs). The study of lncRNAs and the identification of their functions, is still an emerging field in plants but the characterization of some of them indicate that they play an important role in crucial regulatory processes like flowering regulation, and responses to abiotic stress and plant hormones. A second group of lncRNAs present in plants is formed by viroids, exogenous infectious subviral plant pathogens well known since many years. Viroids are composed of circular RNA genomes without protein-coding capacity and subvert enzymatic activities of their hosts to complete its own biological cycle. Different aspects of viroid biology and viroid-host interactions have been elucidated in the last years and some of them are the main topic of this review together with the analysis of the state-of-the-art about the growing field of endogenous lncRNAs in plants. PMID:26319312

  3. Non-coding RNAs: the architects of eukaryotic complexity.

    PubMed

    Mattick, J S

    2001-11-01

    Around 98% of all transcriptional output in humans is non-coding RNA. RNA-mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like RNA interference, co-suppression, transgene silencing, imprinting, methylation, and possibly position-effect variegation and transvection, all involve intersecting pathways based on or connected to RNA signaling. I suggest that the central dogma is incomplete, and that intronic and other non-coding RNAs have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system of trans-acting RNAs that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, RNA-DNA, RNA-RNA and RNA-protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing. PMID:11713189

  4. Non-coding RNAs: Classification, Biology and Functioning.

    PubMed

    Hombach, Sonja; Kretz, Markus

    2016-01-01

    One of the long-standing principles of molecular biology is that DNA acts as a template for transcription of messenger RNAs, which serve as blueprints for protein translation. A rapidly growing number of exceptions to this rule have been reported over the past decades: they include long known classes of RNAs involved in translation such as transfer RNAs and ribosomal RNAs, small nuclear RNAs involved in splicing events, and small nucleolar RNAs mainly involved in the modification of other small RNAs, such as ribosomal RNAs and transfer RNAs. More recently, several classes of short regulatory non-coding RNAs, including piwi-associated RNAs, endogenous short-interfering RNAs and microRNAs have been discovered in mammals, which act as key regulators of gene expression in many different cellular pathways and systems. Additionally, the human genome encodes several thousand long non-protein coding RNAs >200 nucleotides in length, some of which play crucial roles in a variety of biological processes such as epigenetic control of chromatin, promoter-specific gene regulation, mRNA stability, X-chromosome inactivation and imprinting. In this chapter, we will introduce several classes of short and long non-coding RNAs, describe their diverse roles in mammalian gene regulation and give examples for known modes of action. PMID:27573892

  5. Atrazine tolerance mechanism(s) in photoautotrophic potato cells

    SciTech Connect

    Smeda, R.J.; Hasegawa, P.M.; Weller, S.C. )

    1989-04-01

    A photoautotrophic potato cell line (variant) was isolated and is capable of sustained growth in media containing in the herbicide atrazine at concentration up to 100 x greater than the lethal concentration for the unselected (wild type) cell line (1.0 {mu}M). Fresh weight doubling times of variant cells in the presence or absence of 1.0 {mu}M atrazine were identical to wild type cells grown in the absence of atrazine. Maintenance of variant cells up to 10 passages in the absence of atrazine resulted in a reduction in the concentration of atrazine necessary to inhibit fresh weight gain by 99% (ID{sub 99}) from 100 to 80 {mu}M. Comparison of {sup 14}C-atrazine uptake indicated wild type cells accumulated up to 2.5-fold more atrazine than varient cells within 72h of exposure but no differences were detected thereafter. Electron transport of both isolated chloroplasts and intact cells were significantly inhibited in the wild type cell line by 1.0 {mu}M atrazine but unaffected in the variant cell line by atrazine concentrations up to 10 {mu}M. After 30 days in the presence of 1.0 {mu}M atrazine, wild type cells did not significantly metabolize atrazine, however, variant cells reduced atrazine concentrations to <0.05 {mu}M regardless if the initial atrazine concentration was 1.0 or 10.0 {mu}M. Both metabolism of atrazine and alterations within the chloroplast (potentially a reduction in atrazine binding affinity) appear to be important components of tolerance within variant cells.

  6. Regulatory Roles of Non-Coding RNAs in Colorectal Cancer

    PubMed Central

    Wang, Jun; Song, Yong-Xi; Ma, Bin; Wang, Jia-Jun; Sun, Jing-Xu; Chen, Xiao-Wan; Zhao, Jun-Hua; Yang, Yu-Chong; Wang, Zhen-Ning

    2015-01-01

    Non-coding RNAs (ncRNAs) have recently gained attention because of their involvement in different biological processes. An increasing number of studies have demonstrated that mutations or abnormal expression of ncRNAs are closely associated with various diseases including cancer. The present review is a comprehensive examination of the aberrant regulation of ncRNAs in colorectal cancer (CRC) and a summary of the current findings on ncRNAs, including long ncRNAs, microRNAs, small interfering RNAs, small nucleolar RNAs, small nuclear RNAs, Piwi-interacting RNAs, and circular RNAs. These ncRNAs might become novel biomarkers and targets as well as potential therapeutic tools for the treatment of CRC in the near future and this review may provide important clues for further research on CRC and for the selection of effective therapeutic targets. PMID:26307974

  7. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs)

    NASA Technical Reports Server (NTRS)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This report contains the outcome of the assessment and the findings, observations, and NESC recommendations to the Agency and individual NASA Centers.

  8. Non-coding RNAs in DNA damage response

    PubMed Central

    Liu, Yunhua; Lu, Xiongbin

    2012-01-01

    Genome-wide studies have revealed that human and other mammalian genomes are pervasively transcribed and produce thousands of regulatory non-protein-coding RNAs (ncRNAs), including miRNAs, siRNAs, piRNAs and long non-coding RNAs (lncRNAs). Emerging evidences suggest that these ncRNAs also play a pivotal role in genome integrity and stability via the regulation of DNA damage response (DDR). In this review, we discuss the recent finding on the interplay of ncRNAs with the canonical DDR signaling pathway, with a particular emphasis on miRNAs and lncRNAs. While the expression of ncRNAs is regulated in the DDR, the DDR is also subjected to regulation by those DNA damage-responsive ncRNAs. In addition, the roles of those Dicer- and Drosha-dependent small RNAs produced in the vicinity of double-strand breaks sites are also described. PMID:23226613

  9. Non-coding RNAs in mammalian sexual development.

    PubMed

    McFarlane, L; Wilhelm, D

    2009-01-01

    The present decade is witnessing a paradigm shift in our understanding of gene regulation. RNA, once relegated to an intermediary between DNA and protein, has emerged as a key contributor in the coordination of complex developmental pathways. For sexually reproducing organisms, propagation of the species is accomplished via an elaborate sexual phenotype. In mammals this consists of a highly complex cell lineage that has the capacity for intricate self-differentiation whilst maintaining the potential to generate all cell types upon fertilization. In addition, mammals possess a diverse range of somatic reproductive tissues and organs that often undergo dynamic morphological changes in response to a variety of external and internal cues. Although the protein component required to mediate these processes continues to be vigorously investigated, it is becoming increasingly apparent that an understanding of the non-coding RNA (ncRNA) component is required to develop a comprehensive picture of mammalian sexual development. PMID:20197714

  10. Non-coding RNAs Functioning in Colorectal Cancer Stem Cells.

    PubMed

    Fanale, Daniele; Barraco, Nadia; Listì, Angela; Bazan, Viviana; Russo, Antonio

    2016-01-01

    In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main signaling pathways involved in the homeostasis of colorectal (CRC) stem cells are the Wnt, Notch, Sonic Hedgehog, and Bone Morfogenic Protein (BMP) pathways, which are mostly responsible for all the features that have been widely referred to stem cells. The same pathways have been identified in colorectal cancer stem cells (CRCSCs), conferring a more aggressive phenotype compared to non-stem CRC cells. Recently, several evidences suggested that non-coding RNAs (ncRNAs) may play a crucial role in the regulation of different biological mechanisms in CRC, by modulating the expression of critical stem cell transcription factors that have been found active in CSCs. In this chapter, we will discuss the involvement of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in stemness acquisition and maintenance by CRCSCs, through the regulation of pathways modulating the CSC phenotype and growth, carcinogenesis, differentiation, and epithelial to mesenchymal transition (EMT). PMID:27573896

  11. The Non-Coding RNA Ontology (NCRO): a comprehensive resource for the unification of non-coding RNA biology.

    PubMed

    Huang, Jingshan; Eilbeck, Karen; Smith, Barry; Blake, Judith A; Dou, Dejing; Huang, Weili; Natale, Darren A; Ruttenberg, Alan; Huan, Jun; Zimmermann, Michael T; Jiang, Guoqian; Lin, Yu; Wu, Bin; Strachan, Harrison J; He, Yongqun; Zhang, Shaojie; Wang, Xiaowei; Liu, Zixing; Borchert, Glen M; Tan, Ming

    2016-01-01

    In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/ncro.owl. PMID:27152146

  12. Non-coding recurrent mutations in chronic lymphocytic leukaemia.

    PubMed

    Puente, Xose S; Beà, Silvia; Valdés-Mas, Rafael; Villamor, Neus; Gutiérrez-Abril, Jesús; Martín-Subero, José I; Munar, Marta; Rubio-Pérez, Carlota; Jares, Pedro; Aymerich, Marta; Baumann, Tycho; Beekman, Renée; Belver, Laura; Carrio, Anna; Castellano, Giancarlo; Clot, Guillem; Colado, Enrique; Colomer, Dolors; Costa, Dolors; Delgado, Julio; Enjuanes, Anna; Estivill, Xavier; Ferrando, Adolfo A; Gelpí, Josep L; González, Blanca; González, Santiago; González, Marcos; Gut, Marta; Hernández-Rivas, Jesús M; López-Guerra, Mónica; Martín-García, David; Navarro, Alba; Nicolás, Pilar; Orozco, Modesto; Payer, Ángel R; Pinyol, Magda; Pisano, David G; Puente, Diana A; Queirós, Ana C; Quesada, Víctor; Romeo-Casabona, Carlos M; Royo, Cristina; Royo, Romina; Rozman, María; Russiñol, Nuria; Salaverría, Itziar; Stamatopoulos, Kostas; Stunnenberg, Hendrik G; Tamborero, David; Terol, María J; Valencia, Alfonso; López-Bigas, Nuria; Torrents, David; Gut, Ivo; López-Guillermo, Armando; López-Otín, Carlos; Campo, Elías

    2015-10-22

    Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to ≥4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia. PMID:26200345

  13. Long Non-Coding RNAs in Endometrial Carcinoma

    PubMed Central

    Smolle, Maria A.; Bullock, Marc D.; Ling, Hui; Pichler, Martin; Haybaeck, Johannes

    2015-01-01

    Endometrial carcinoma (EC), the second most common form of gynaecological malignancy, can be divided into two distinct sub-types: Type I tumours arise from hyperplastic endometrium and typically effect women around the time of menopause, whereas type II tumours arise in postmenopausal women from atrophic endometrium. Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding molecules that have recently been implicated in the pathogenesis of many types of cancer including gynaecological tumours. Although they play critical physiological roles in cellular metabolism, their expression and function are deregulated in EC compared with paired normal tissue, indicating that they may also participate in tumour initiation and progression. For instance, the lncRNA MALAT-1 is down-regulated in EC samples compared to normal or hyperplastic endometrium, whereas the lncRNA OVAL is down-regulated in type II disease but up-regulated in type I disease. Other notatble lncRNAs such as HOTAIR, H19 and SRA become up-regulated with increasing EC tumour grade and other features associated with poor prognosis. In the current review, we will examine the growing body of evidence linking deregulated lncRNAs with specific biological functions of tumour cells in EC, we will highlight associations between lncRNAs and the molecular pathways implicated in EC tumourigenesis and we will identify critical knowledge gaps that remain to be addressed. PMID:26556343

  14. Non-coding RNA in Ovarian Development and Disease.

    PubMed

    Fitzgerald, J Browning; George, Jitu; Christenson, Lane K

    2016-01-01

    The ovary's primary function is to produce the mature female gamete, the oocyte that, following fertilization, can develop into an embryo, implant within the uterus and ultimately allow the mother's genetic material to be passed along to subsequent generations. In addition to supporting the generation of the oocyte, the ovary and specific ephemeral tissues within it, follicles and corpora lutea, produce steroids that regulate all aspects of the reproductive system, including the hypothalamic/pituitary axis, the reproductive tract (uterus, oviduct, cervix), secondary sex characteristics all of which are also essential for pregnancy and subsequent nurturing of the offspring. To accomplish these critical roles, ovarian development and function are tightly regulated by a number of exogenous (hypothalamic/pituitary) and endogenous (intraovarian) hormones. Within ovarian cells, intricate signalling cascades and transcriptional and post-transcriptional gene regulatory networks respond to these hormonal influences to provide the exquisite control over all of the temporal and spatial events that must be synchronized to allow this organ to successfully complete its function. This book chapter will focus specifically on the role of non-coding RNAs, their identification and described functional roles within the ovary with respect to normal function and their possible involvement in diseases, which involve the ovary. PMID:26659488

  15. Long non-coding RNA expression in primary human monocytes.

    PubMed

    Mirsafian, Hoda; Manda, Srinivas Srikanth; Mitchell, Christopher J; Sreenivasamurthy, Sreelakshmi; Ripen, Adiratna Mat; Mohamad, Saharuddin Bin; Merican, Amir Feisal; Pandey, Akhilesh

    2016-07-01

    Long non-coding RNAs (lncRNAs) have been shown to possess a wide range of functions in both cellular and developmental processes including cancers. Although some of the lncRNAs have been implicated in the regulation of the immune response, the exact function of the large majority of lncRNAs still remains unknown. In this study, we characterized the lncRNAs in human primary monocytes, an essential component of the innate immune system. We performed RNA sequencing of monocytes from four individuals and combined our data with eleven other publicly available datasets. Our analysis led to identification of ~8000 lncRNAs of which >1000 have not been previously reported in monocytes. PCR-based validation of a subset of the identified novel long intergenic noncoding RNAs (lincRNAs) revealed distinct expression patterns. Our study provides a landscape of lncRNAs in monocytes, which could facilitate future experimental studies to characterize the functions of these molecules in the innate immune system. PMID:26778813

  16. Non-coding RNAs, the cutting edge of histone messages

    PubMed Central

    Köhn, Marcel; Hüttelmaier, Stefan

    2016-01-01

    ABSTRACT In metazoan the 3′-end processing of histone mRNAs is a conserved process involving the concerted action of many protein factors and the non-coding U7 snRNA. Recently, we identified that the processing of histone pre-mRNAs is promoted by an additional ncRNA, the Y3-derived Y3** RNA. U7 modulates the association of the U7 snRNP whereas Y3** promotes recruitment of CPSF (cleavage and polyadenylation specific factor) proteins to nascent histone transcripts at histone locus bodies (HLBs) in mammals. This enhances the 3′-end cleavage of nascent histone pre-mRNAs and modulates HLB assembly. Here we discuss new insights in the role of ncRNAs in the spatiotemporal control of histone synthesis. We propose that ncRNAs scaffold the formation of functional protein-RNA complexes and their sequential deposition on nascent histone pre-mRNAs at HLBs. These findings add to the multiple roles of ncRNAs in controlling gene expression and may provide new avenues for targeting histone synthesis in cancer. PMID:26909464

  17. Identification and function of long non-coding RNA

    PubMed Central

    Ernst, Carl; Morton, Cynthia C.

    2013-01-01

    Long non-coding (lnc) RNAs are defined as non-protein coding RNAs distinct from housekeeping RNAs such as tRNAs, rRNAs, and snRNAs, and independent from small RNAs with specific molecular processing machinery such as micro- or piwi-RNAs. Recent studies of lncRNAs across different species have revealed a diverse population of RNA molecules of differing size and function. RNA sequencing studies suggest transcription throughout the genome, so there is a need to understand how sequence relates to functional and structural relationships amongst RNA molecules. Our synthesis of recent studies suggests that neither size, presence of a poly-A tail, splicing, direction of transcription, nor strand specificity are of importance to lncRNA function. Rather, relative genomic position in relation to a target is fundamentally important. In this review, we describe issues of key importance in functional assessment of lncRNA and how this might apply to lncRNAs important in neurodevelopment. PMID:24106460

  18. Melanoma addiction to the long non-coding RNA SAMMSON.

    PubMed

    Leucci, Eleonora; Vendramin, Roberto; Spinazzi, Marco; Laurette, Patrick; Fiers, Mark; Wouters, Jasper; Radaelli, Enrico; Eyckerman, Sven; Leonelli, Carina; Vanderheyden, Katrien; Rogiers, Aljosja; Hermans, Els; Baatsen, Pieter; Aerts, Stein; Amant, Frederic; Van Aelst, Stefan; van den Oord, Joost; de Strooper, Bart; Davidson, Irwin; Lafontaine, Denis L J; Gevaert, Kris; Vandesompele, Jo; Mestdagh, Pieter; Marine, Jean-Christophe

    2016-03-24

    Focal amplifications of chromosome 3p13-3p14 occur in about 10% of melanomas and are associated with a poor prognosis. The melanoma-specific oncogene MITF resides at the epicentre of this amplicon. However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA (lncRNA) gene SAMMSON is consistently co-gained with MITF. In addition, SAMMSON is a target of the lineage-specific transcription factor SOX10 and its expression is detectable in more than 90% of human melanomas. Whereas exogenous SAMMSON increases the clonogenic potential in trans, SAMMSON knockdown drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state and BRAF, NRAS or TP53 mutational status. Moreover, SAMMSON targeting sensitizes melanoma to MAPK-targeting therapeutics both in vitro and in patient-derived xenograft models. Mechanistically, SAMMSON interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that silencing of the lineage addiction oncogene SAMMSON disrupts vital mitochondrial functions in a cancer-cell-specific manner; this silencing is therefore expected to deliver highly effective and tissue-restricted anti-melanoma therapeutic responses. PMID:27008969

  19. Long non-coding RNAs in colorectal cancer

    PubMed Central

    Xie, Xia; Tang, Bo; Xiao, Yu-Feng; Xie, Rui; Li, Bo-Sheng; Dong, Hui; Zhou, Jian-Yun; Yang, Shi-Ming

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Despite substantial progress in understanding the molecular mechanisms and treatment of CRC in recent years, the overall survival rate of CRC patients has not improved dramatically. The development of CRC is multifactor and multistep processes, in which abnormal gene expression may play an important role. With the advance of human tumor molecular biology, a series of studies have highlighted the role of long non-coding RNAs (lncRNAs) in the development of CRC. CRC-related lncRNAs have been demonstrated to regulate the genes by various mechanisms, including epigenetic modifications, lncRNA-miRNA and lncRNA-protein interactions, and by their actions as miRNA precursors or pseudogenes. Since some lncRNAs can be detected in human body fluid and have good specificity and accessibility, they have been suggested to be used as novel potential biomarkers for CRC diagnosis and prognosis as well as in the prediction of the response to therapy. Therefore, in this review, we will focus on lncRNAs in CRC development, the mechanisms and biomarkers of lncRNAs in CRC. PMID:26637808

  20. Associating schizophrenia, long non-coding RNAs and neurostructural dynamics

    PubMed Central

    Merelo, Veronica; Durand, Dante; Lescallette, Adam R.; Vrana, Kent E.; Hong, L. Elliot; Faghihi, Mohammad Ali; Bellon, Alfredo

    2015-01-01

    Several lines of evidence indicate that schizophrenia has a strong genetic component. But the exact nature and functional role of this genetic component in the pathophysiology of this mental illness remains a mystery. Long non-coding RNAs (lncRNAs) are a recently discovered family of molecules that regulate gene transcription through a variety of means. Consequently, lncRNAs could help us bring together apparent unrelated findings in schizophrenia; namely, genomic deficiencies on one side and neuroimaging, as well as postmortem results on the other. In fact, the most consistent finding in schizophrenia is decreased brain size together with enlarged ventricles. This anomaly appears to originate from shorter and less ramified dendrites and axons. But a decrease in neuronal arborizations cannot explain the complex pathophysiology of this psychotic disorder; however, dynamic changes in neuronal structure present throughout life could. It is well recognized that the structure of developing neurons is extremely plastic. This structural plasticity was thought to stop with brain development. However, breakthrough discoveries have shown that neuronal structure retains some degree of plasticity throughout life. What the neuroscientific field is still trying to understand is how these dynamic changes are regulated and lncRNAs represent promising candidates to fill this knowledge gap. Here, we present evidence that associates specific lncRNAs with schizophrenia. We then discuss the potential role of lncRNAs in neurostructural dynamics. Finally, we explain how dynamic neurostructural modifications present throughout life could, in theory, reconcile apparent unrelated findings in schizophrenia. PMID:26483630

  1. Neighboring Gene Regulation by Antisense Long Non-Coding RNAs

    PubMed Central

    Villegas, Victoria E.; Zaphiropoulos, Peter G.

    2015-01-01

    Antisense transcription, considered until recently as transcriptional noise, is a very common phenomenon in human and eukaryotic transcriptomes, operating in two ways based on whether the antisense RNA acts in cis or in trans. This process can generate long non-coding RNAs (lncRNAs), one of the most diverse classes of cellular transcripts, which have demonstrated multifunctional roles in fundamental biological processes, including embryonic pluripotency, differentiation and development. Antisense lncRNAs have been shown to control nearly every level of gene regulation—pretranscriptional, transcriptional and posttranscriptional—through DNA–RNA, RNA–RNA or protein–RNA interactions. This review is centered on functional studies of antisense lncRNA-mediated regulation of neighboring gene expression. Specifically, it addresses how these transcripts interact with other biological molecules, nucleic acids and proteins, to regulate gene expression through chromatin remodeling at the pretranscriptional level and modulation of transcriptional and post-transcriptional processes by altering the sense mRNA structure or the cellular compartmental distribution, either in the nucleus or the cytoplasm. PMID:25654223

  2. Non-coding Y RNAs as tethers and gates

    PubMed Central

    Wolin, Sandra L; Belair, Cedric; Boccitto, Marco; Chen, Xinguo; Sim, Soyeong; Taylor, David W; Wang, Hong-Wei

    2013-01-01

    Non-coding RNAs (ncRNAs) called Y RNAs are abundant components of both animal cells and a variety of bacteria. In all species examined, these ~100 nt RNAs are bound to the Ro 60 kDa (Ro60) autoantigen, a ring-shaped protein that also binds misfolded ncRNAs in some vertebrate nuclei. Although the function of Ro60 RNPs has been mysterious, we recently reported that a bacterial Y RNA tethers Ro60 to the 3′ to 5′ exoribonuclease polynucleotide phosphorylase (PNPase) to form RYPER (Ro60/Y RNA/PNPase Exoribonuclease RNP), a new RNA degradation machine. PNPase is a homotrimeric ring that degrades single-stranded RNA, and Y RNA-mediated tethering of Ro60 increases the effectiveness of PNPase in degrading structured RNAs. Single particle electron microscopy of RYPER suggests that RNA threads through the Ro60 ring into the PNPase cavity. Further studies indicate that Y RNAs may also act as gates to regulate entry of RNA substrates into the Ro60 channel. These findings reveal novel functions for Y RNAs and raise questions about how the bacterial findings relate to the roles of these ncRNAs in animal cells. Here we review the literature on Y RNAs, highlighting their close relationship with Ro60 proteins and the hypothesis that these ncRNAs function generally to tether Ro60 rings to diverse RNA-binding proteins. PMID:24036917

  3. Long non-coding RNAs in cancer drug resistance development.

    PubMed

    Majidinia, Maryam; Yousefi, Bahman

    2016-09-01

    The presence or emergence of chemoresistance in tumor cells is a major burden in cancer therapy. While drug resistance is a multifactorial phenomenon arising from altered membrane transport of drugs, altered drug metabolism, altered DNA repair, reduced apoptosis rate and alterations of drug metabolism, it can also be linked to genetic and epigenetic factors. Long non-coding RNAs (lncRNAs) have important regulatory roles in many aspects of genome function including gene transcription, splicing, and epigenetics as well as biological processes involved in cell cycle, cell differentiation, development, and pluripotency. As such, it may not be surprising that some lncRNAs have been recently linked to carcinogenesis and drug resistance/sensitivity. Research is accelerating to decipher the exact molecular mechanism of lncRNA-regulated drug resistance and its therapeutic implications. In this article, we will review the structure, biogenesis, and mode of action of lncRNAs. Then, the involvement of lncRNAs in drug resistance will be discussed in detail. PMID:27427176

  4. Non-coding RNAs, the cutting edge of histone messages.

    PubMed

    Köhn, Marcel; Hüttelmaier, Stefan

    2016-04-01

    In metazoan the 3'-end processing of histone mRNAs is a conserved process involving the concerted action of many protein factors and the non-coding U7 snRNA. Recently, we identified that the processing of histone pre-mRNAs is promoted by an additional ncRNA, the Y3-derived Y3** RNA. U7 modulates the association of the U7 snRNP whereas Y3** promotes recruitment of CPSF (cleavage and polyadenylation specific factor) proteins to nascent histone transcripts at histone locus bodies (HLBs) in mammals. This enhances the 3'-end cleavage of nascent histone pre-mRNAs and modulates HLB assembly. Here we discuss new insights in the role of ncRNAs in the spatiotemporal control of histone synthesis. We propose that ncRNAs scaffold the formation of functional protein-RNA complexes and their sequential deposition on nascent histone pre-mRNAs at HLBs. These findings add to the multiple roles of ncRNAs in controlling gene expression and may provide new avenues for targeting histone synthesis in cancer. PMID:26909464

  5. Long Non-Coding RNAs in Haematological Malignancies

    PubMed Central

    Garitano-Trojaola, Andoni; Agirre, Xabier; Prósper, Felipe; Fortes, Puri

    2013-01-01

    Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. LncRNAs are as diverse as mRNAs and they normally share the same biosynthetic machinery based on RNA polymerase II, splicing and polyadenylation. However, lncRNAs have low coding potential. Compared to mRNAs, lncRNAs are preferentially nuclear, more tissue specific and expressed at lower levels. Most of the lncRNAs described to date modulate the expression of specific genes by guiding chromatin remodelling factors; inducing chromosomal loopings; affecting transcription, splicing, translation or mRNA stability; or serving as scaffolds for the organization of cellular structures. They can function in cis, cotranscriptionally, or in trans, acting as decoys, scaffolds or guides. These functions seem essential to allow cell differentiation and growth. In fact, many lncRNAs have been shown to exert oncogenic or tumor suppressor properties in several cancers including haematological malignancies. In this review, we summarize what is known about lncRNAs, the mechanisms for their regulation in cancer and their role in leukemogenesis, lymphomagenesis and hematopoiesis. Furthermore, we discuss the potential of lncRNAs in diagnosis, prognosis and therapy in cancer, with special attention to haematological malignancies. PMID:23887658

  6. Ageing and the Small, Non-Coding RNA World

    PubMed Central

    Kato, Masaomi; Slack, Frank J.

    2012-01-01

    MicroRNAs, a class of small, non-coding RNAs, are now widely known for their importance in many aspects of biology. These small regulatory RNAs have critical functions in diverse biological events, including development and disease. Recent findings show that microRNAs are essential for lifespan determination in the model organisms, C. elegans and Drosophila, suggesting that microRNAs are also involved in the complex process of ageing. Further, short RNA fragments derived from longer parental RNAs, such as transfer RNA cleavage fragments, have now emerged as a novel class of regulatory RNAs that inhibit translation in response to stress. In addition, the RNA editing pathway is likely to act in the double-stranded RNA-mediated silencing machinery to suppress unfavorable RNA interference activity in the ageing process. These multiple, redundant layers in gene regulatory networks may make it possible to both stably and flexibly regulate genetic pathways in ensuring robustness of developmental and ageing processes. PMID:22504407

  7. Community structure of non-coding RNA interaction network.

    PubMed

    Nacher, Jose C

    2013-01-01

    Rapid technological advances have shown that the ratio of non-protein coding genes rises to 98.5% in humans, suggesting that current knowledge on genetic information processing might be largely incomplete. It implies that protein-coding sequences only represent a small fraction of cellular transcriptional information. Here, we examine the community structure of the network defined by functional interactions between non-coding RNAs (ncRNAs) and proteins related bio-macromolecules (PRMs) using a two-fold approach: modularity in bipartite network and k-clique community detection. First, the high modularity scores as well as the distribution of community sizes showing a scaling-law revealed manifestly non-random features. Second, the k-clique sub-graphs and overlaps show that the identified communities of the ncRNA molecules of H. sapiens can potentially be associated with certain functions. These findings highlight the complex modular structure of ncRNA interactions and its possible regulatory roles in the cell. PMID:23545211

  8. CANTATAdb: A Collection of Plant Long Non-Coding RNAs

    PubMed Central

    Szcześniak, Michał W.; Rosikiewicz, Wojciech; Makałowska, Izabela

    2016-01-01

    Long non-coding RNAs (lncRNAs) represent a class of potent regulators of gene expression that are found in a wide array of eukaryotes; however, our knowledge about these molecules in plants is still very limited. In particular, a number of model plant species still lack comprehensive data sets of lncRNAs and their annotations, and very little is known about their biological roles. To meet these shortcomings, we created an online database of lncRNAs in 10 model plant species. The lncRNAs were identified computationally using dozens of publicly available RNA sequencing (RNA-Seq) libraries. Expression values, coding potential, sequence alignments as well as other types of data provide annotation for the identified lncRNAs. In order to better characterize them, we investigated their potential roles in splicing modulation and deregulation of microRNA functions. The data are freely available for searching, browsing and downloading from an online database called CANTATAdb (http://cantata.amu.edu.pl, http://yeti.amu.edu.pl/CANTATA/). PMID:26657895

  9. Perspectives of Long Non-Coding RNAs in Cancer Diagnostics

    PubMed Central

    Reis, Eduardo M.; Verjovski-Almeida, Sergio

    2012-01-01

    Long non-coding RNAs (lncRNAs) transcribed from intergenic and intronic regions of the human genome constitute a broad class of cellular transcripts that are under intensive investigation. While only a handful of lncRNAs have been characterized, their involvement in fundamental cellular processes that control gene expression highlights a central role in cell homeostasis. Not surprisingly, aberrant expression of regulatory lncRNAs has been increasingly documented in different types of cancer, where they can mediate both oncogenic or tumor suppressor effects. Interaction with chromatin remodeling complexes that promote silencing of specific genes or modulation of splicing factor proteins seem to be two general modes of lncRNA regulation, but it is conceivable that additional mechanisms of action are yet to be unveiled. LncRNAs show greater tissue specificity compared to protein-coding mRNAs making them attractive in the search of novel diagnostics/prognostics cancer biomarkers in body fluid samples. In fact, lncRNA prostate cancer antigen 3 can be detected in urine samples and has been shown to improve diagnosis of prostate cancer. We suggest that an unbiased screening of the presence of RNAs in easily accessible body fluids such as serum and urine might reveal novel circulating lncRNAs as potential biomarkers in many types of cancer. Annotation and functional characterization of the lncRNA complement of the cancer transcriptome will conceivably provide new venues for early diagnosis and treatment of the disease. PMID:22408643

  10. Long Non-Coding RNAs: Critical Players in Hepatocellular Carcinoma

    PubMed Central

    Sun, Jin; Bie, Beibei; Zhang, Shu; Yang, Jun; Li, Zongfang

    2014-01-01

    Hepatocellular carcinoma (HCC) is a complex disease with multiple underlying pathogenic mechanisms caused by a variety of etiologic factors. Emerging evidence showed that long non-coding RNAs (lncRNAs), with size larger than 200 nucleotides (nt), play important roles in various types of cancer development and progression. In recent years, some dysregulated lncRNAs in HCC have been revealed and roles for several of them in HCC have been characterized. All these findings point to the potential of lncRNAs as prospective novel therapeutic targets in HCC. In this review, we summarize known dysregulated lncRNAs in HCC, and review potential biological roles and underlying molecular mechanisms of lncRNAs in HCC. Additionally, we discussed prospects of lncRNAs as potential biomarker and therapeutic target for HCC. In conclusion, this paper will help us gain better understanding of molecular mechanisms by which lncRNAs perform their function in HCC and also provide general strategies and directions for future research. PMID:25387074

  11. Non-coding RNAs and complex distributed genetic networks

    NASA Astrophysics Data System (ADS)

    Zhdanov, Vladimir P.

    2011-08-01

    In eukaryotic cells, the mRNA-protein interplay can be dramatically influenced by non-coding RNAs (ncRNAs). Although this new paradigm is now widely accepted, an understanding of the effect of ncRNAs on complex genetic networks is lacking. To clarify what may happen in this case, we propose a mean-field kinetic model describing the influence of ncRNA on a complex genetic network with a distributed architecture including mutual protein-mediated regulation of many genes transcribed into mRNAs. ncRNA is considered to associate with mRNAs and inhibit their translation and/or facilitate degradation. Our results are indicative of the richness of the kinetics under consideration. The main complex features are found to be bistability and oscillations. One could expect to find kinetic chaos as well. The latter feature has however not been observed in our calculations. In addition, we illustrate the difference in the regulation of distributed networks by mRNA and ncRNA.

  12. Biocomputational prediction of small non-coding RNAs in Streptomyces

    PubMed Central

    Pánek, Josef; Bobek, Jan; Mikulík, Karel; Basler, Marek; Vohradský, Jiří

    2008-01-01

    Background The first systematic study of small non-coding RNAs (sRNA, ncRNA) in Streptomyces is presented. Except for a few exceptions, the Streptomyces sRNAs, as well as the sRNAs in other genera of the Actinomyces group, have remained unstudied. This study was based on sequence conservation in intergenic regions of Streptomyces, localization of transcription termination factors, and genomic arrangement of genes flanking the predicted sRNAs. Results Thirty-two potential sRNAs in Streptomyces were predicted. Of these, expression of 20 was detected by microarrays and RT-PCR. The prediction was validated by a structure based computational approach. Two predicted sRNAs were found to be terminated by transcription termination factors different from the Rho-independent terminators. One predicted sRNA was identified computationally with high probability as a Streptomyces 6S RNA. Out of the 32 predicted sRNAs, 24 were found to be structurally dissimilar from known sRNAs. Conclusion Streptomyces is the largest genus of Actinomyces, whose sRNAs have not been studied. The Actinomyces is a group of bacterial species with unique genomes and phenotypes. Therefore, in Actinomyces, new unique bacterial sRNAs may be identified. The sequence and structural dissimilarity of the predicted Streptomyces sRNAs demonstrated by this study serve as the first evidence of the uniqueness of Actinomyces sRNAs. PMID:18477385

  13. Environmental Health and Long Non-coding RNAs.

    PubMed

    Karlsson, Oskar; Baccarelli, Andrea A

    2016-09-01

    An individual's risk of developing a common disease typically depends on an interaction of genetic and environmental factors. Epigenetic research is uncovering novel ways through which environmental factors such as diet, air pollution, and chemical exposure can affect our genes. DNA methylation and histone modifications are the most commonly studied epigenetic mechanisms. The role of long non-coding RNAs (lncRNAs) in epigenetic processes has been more recently highlighted. LncRNAs are defined as transcribed RNA molecules greater than 200 nucleotides in length with little or no protein-coding capability. While few functional lncRNAs have been well characterized to date, they have been demonstrated to control gene regulation at every level, including transcriptional gene silencing via regulation of the chromatin structure and DNA methylation. This review aims to provide a general overview of lncRNA function with a focus on their role as key regulators of health and disease and as biomarkers of environmental exposure. PMID:27234044

  14. The most frequent short sequences in non-coding DNA.

    PubMed

    Subirana, Juan A; Messeguer, Xavier

    2010-03-01

    The purpose of this work is to determine the most frequent short sequences in non-coding DNA. They may play a role in maintaining the structure and function of eukaryotic chromosomes. We present a simple method for the detection and analysis of such sequences in several genomes, including Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens. We also study two chromosomes of man and mouse with a length similar to the whole genomes of the other species. We provide a list of the most common sequences of 9-14 bases in each genome. As expected, they are present in human Alu sequences. Our programs may also give a graph and a list of their position in the genome. Detection of clusters is also possible. In most cases, these sequences contain few alternating regions. Their intrinsic structure and their influence on nucleosome formation are not known. In particular, we have found new features of short sequences in C. elegans, which are distributed in heterogeneous clusters. They appear as punctuation marks in the chromosomes. Such clusters are not found in either A. thaliana or D. melanogaster. We discuss the possibility that they play a role in centromere function and homolog recognition in meiosis. PMID:19966278

  15. Sequence and Structural Analyses for Functional Non-coding RNAs

    NASA Astrophysics Data System (ADS)

    Sakakibara, Yasubumi; Sato, Kengo

    Analysis and detection of functional RNAs are currently important topics in both molecular biology and bioinformatics research. Several computational methods based on stochastic context-free grammars (SCFGs) have been developed for modeling and analysing functional RNA sequences. These grammatical methods have succeeded in modeling typical secondary structures of RNAs and are used for structural alignments of RNA sequences. Such stochastic models, however, are not sufficient to discriminate member sequences of an RNA family from non-members, and hence to detect non-coding RNA regions from genome sequences. Recently, the support vector machine (SVM) and kernel function techniques have been actively studied and proposed as a solution to various problems in bioinformatics. SVMs are trained from positive and negative samples and have strong, accurate discrimination abilities, and hence are more appropriate for the discrimination tasks. A few kernel functions that extend the string kernel to measure the similarity of two RNA sequences from the viewpoint of secondary structures have been proposed. In this article, we give an overview of recent progress in SCFG-based methods for RNA sequence analysis and novel kernel functions tailored to measure the similarity of two RNA sequences and developed for use with support vector machines (SVM) in discriminating members of an RNA family from non-members.

  16. Non-coding RNA: a new frontier in regulatory biology

    PubMed Central

    Fu, Xiang-Dong

    2015-01-01

    A striking finding in the past decade is the production of numerous non-coding RNAs (ncRNAs) from mammalian genomes. While it is entirely possible that many of those ncRNAs are transcription noises or by-products of RNA processing, increasing evidence suggests that a large fraction of them are functional and provide various regulatory activities in the cell. Thus, functional genomics and proteomics are incomplete without understanding functional ribonomics. As has been long suggested by the ‘RNA world’ hypothesis, many ncRNAs have the capacity to act like proteins in diverse biochemical processes. The enormous amount of information residing in the primary sequences and secondary structures of ncRNAs makes them particularly suited to function as scaffolds for molecular interactions. In addition, their functions appear to be stringently controlled by default via abundant nucleases when not engaged in specific interactions. This review focuses on the functional properties of regulatory ncRNAs in comparison with proteins and emphasizes both the opportunities and challenges in future ncRNA research. PMID:25821635

  17. Non-coding RNAs and disease: the classical ncRNAs make a comeback.

    PubMed

    de Almeida, Rogerio Alves; Fraczek, Marcin G; Parker, Steven; Delneri, Daniela; O'Keefe, Raymond T

    2016-08-15

    Many human diseases have been attributed to mutation in the protein coding regions of the human genome. The protein coding portion of the human genome, however, is very small compared with the non-coding portion of the genome. As such, there are a disproportionate number of diseases attributed to the coding compared with the non-coding portion of the genome. It is now clear that the non-coding portion of the genome produces many functional non-coding RNAs and these RNAs are slowly being linked to human diseases. Here we discuss examples where mutation in classical non-coding RNAs have been attributed to human disease and identify the future potential for the non-coding portion of the genome in disease biology. PMID:27528754

  18. [Role of non-coding regulatory ribonucleic acids in chronic inflammatory diseases].

    PubMed

    Heinz, G A; Mashreghi, M-F

    2016-05-01

    Non-coding regulatory ribonucleic acids (RNA), including microRNA, long non-coding RNA and circular RNA, can influence the expression of genes mediating inflammatory processes and therefore affect the course and progression of chronic inflammatory diseases. Recent studies using antisense oligonucleotides suggest that such non-coding regulatory RNAs are suitable as novel therapeutic target molecules for the treatment of inflammatory rheumatic diseases. PMID:27115697

  19. Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy

    PubMed Central

    Han Li, Chi; Chen, Yangchao

    2015-01-01

    Non-coding RNA refers to a large group of endogenous RNA molecules that have no protein coding capacity, while having specialized cellular and molecular functions. They possess wide range of functions such as the regulation of gene transcription and translation, post-transcriptional modification, epigenetic landscape establishment, protein scaffolding and cofactors recruitments. They are further divided into small non-coding RNAs with size < 200nt (e.g. miRNA, piRNA) and long non-coding RNAs with size >= 200nt (e.g. lincRNA, NAT). Increasing evidences suggest that both non-coding RNAs groups play important roles in cancer development, progression and pathology. Clinically, non-coding RNAs aberrations show high diagnostic and prognostic values. With improved understanding of the nature and roles of non-coding RNAs, it is believed that we can develop therapeutic treatment against cancer via the modulation of these RNA molecules. Advances in nucleic acid drug technology and computational simulation prompt the development of agents to intervene the malignant effects of non-coding RNAs. In this review, we will discuss the role of non-coding RNAs in cancer, and evaluate the potential of non-coding RNA-based cancer therapies. PMID:27047252

  20. Systematic classification of non-coding RNAs by epigenomic similarity

    PubMed Central

    2013-01-01

    Background Even though only 1.5% of the human genome is translated into proteins, recent reports indicate that most of it is transcribed into non-coding RNAs (ncRNAs), which are becoming the subject of increased scientific interest. We hypothesized that examining how different classes of ncRNAs co-localized with annotated epigenomic elements could help understand the functions, regulatory mechanisms, and relationships among ncRNA families. Results We examined 15 different ncRNA classes for statistically significant genomic co-localizations with cell type-specific chromatin segmentation states, transcription factor binding sites (TFBSs), and histone modification marks using GenomeRunner (http://www.genomerunner.org). P-values were obtained using a Chi-square test and corrected for multiple testing using the Benjamini-Hochberg procedure. We clustered and visualized the ncRNA classes by the strength of their statistical enrichments and depletions. We found piwi-interacting RNAs (piRNAs) to be depleted in regions containing activating histone modification marks, such as H3K4 mono-, di- and trimethylation, H3K27 acetylation, as well as certain TFBSs. piRNAs were further depleted in active promoters, weak transcription, and transcription elongation regions, and enriched in repressed and heterochromatic regions. Conversely, transfer RNAs (tRNAs) were depleted in heterochromatin regions and strongly enriched in regions containing activating H3K4 di- and trimethylation marks, H2az histone variant, and a variety of TFBSs. Interestingly, regions containing CTCF insulator protein binding sites were associated with tRNAs. tRNAs were also enriched in the active, weak and poised promoters and, surprisingly, in regions with repetitive/copy number variations. Conclusions Searching for statistically significant associations between ncRNA classes and epigenomic elements permits detection of potential functional and/or regulatory relationships among ncRNA classes, and suggests cell

  1. Kinetic models of gene expression including non-coding RNAs

    NASA Astrophysics Data System (ADS)

    Zhdanov, Vladimir P.

    2011-03-01

    In cells, genes are transcribed into mRNAs, and the latter are translated into proteins. Due to the feedbacks between these processes, the kinetics of gene expression may be complex even in the simplest genetic networks. The corresponding models have already been reviewed in the literature. A new avenue in this field is related to the recognition that the conventional scenario of gene expression is fully applicable only to prokaryotes whose genomes consist of tightly packed protein-coding sequences. In eukaryotic cells, in contrast, such sequences are relatively rare, and the rest of the genome includes numerous transcript units representing non-coding RNAs (ncRNAs). During the past decade, it has become clear that such RNAs play a crucial role in gene expression and accordingly influence a multitude of cellular processes both in the normal state and during diseases. The numerous biological functions of ncRNAs are based primarily on their abilities to silence genes via pairing with a target mRNA and subsequently preventing its translation or facilitating degradation of the mRNA-ncRNA complex. Many other abilities of ncRNAs have been discovered as well. Our review is focused on the available kinetic models describing the mRNA, ncRNA and protein interplay. In particular, we systematically present the simplest models without kinetic feedbacks, models containing feedbacks and predicting bistability and oscillations in simple genetic networks, and models describing the effect of ncRNAs on complex genetic networks. Mathematically, the presentation is based primarily on temporal mean-field kinetic equations. The stochastic and spatio-temporal effects are also briefly discussed.

  2. Effective knockdown of Drosophila long non-coding RNAs by CRISPR interference.

    PubMed

    Ghosh, Sanjay; Tibbit, Charlotte; Liu, Ji-Long

    2016-05-19

    Long non-coding RNAs (lncRNAs) have emerged as regulators of gene expression across metazoa. Interestingly, some lncRNAs function independently of their transcripts - the transcription of the lncRNA locus itself affects target genes. However, current methods of loss-of-function analysis are insufficient to address the role of lncRNA transcription from the transcript which has impeded analysis of their function. Using the minimal CRISPR interference (CRISPRi) system, we show that coexpression of the catalytically inactive Cas9 (dCas9) and guide RNAs targeting the endogenous roX locus in the Drosophila cells results in a robust and specific knockdown of roX1 and roX2 RNAs, thus eliminating the need for recruiting chromatin modifying proteins for effective gene silencing. Additionally, we find that the human and Drosophila codon optimized dCas9 genes are functional and show similar transcription repressive activity. Finally, we demonstrate that the minimal CRISPRi system suppresses roX transcription efficiently in vivo resulting in loss-of-function phenotype, thus validating the method for the first time in a multicelluar organism. Our analysis expands the genetic toolkit available for interrogating lncRNA function in situ and is adaptable for targeting multiple genes across model organisms. PMID:26850642

  3. Effective knockdown of Drosophila long non-coding RNAs by CRISPR interference

    PubMed Central

    Ghosh, Sanjay; Tibbit, Charlotte; Liu, Ji-Long

    2016-01-01

    Long non-coding RNAs (lncRNAs) have emerged as regulators of gene expression across metazoa. Interestingly, some lncRNAs function independently of their transcripts – the transcription of the lncRNA locus itself affects target genes. However, current methods of loss-of-function analysis are insufficient to address the role of lncRNA transcription from the transcript which has impeded analysis of their function. Using the minimal CRISPR interference (CRISPRi) system, we show that coexpression of the catalytically inactive Cas9 (dCas9) and guide RNAs targeting the endogenous roX locus in the Drosophila cells results in a robust and specific knockdown of roX1 and roX2 RNAs, thus eliminating the need for recruiting chromatin modifying proteins for effective gene silencing. Additionally, we find that the human and Drosophila codon optimized dCas9 genes are functional and show similar transcription repressive activity. Finally, we demonstrate that the minimal CRISPRi system suppresses roX transcription efficiently in vivo resulting in loss-of-function phenotype, thus validating the method for the first time in a multicelluar organism. Our analysis expands the genetic toolkit available for interrogating lncRNA function in situ and is adaptable for targeting multiple genes across model organisms. PMID:26850642

  4. Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches.

    PubMed

    Beermann, Julia; Piccoli, Maria-Teresa; Viereck, Janika; Thum, Thomas

    2016-10-01

    Advances in RNA-sequencing techniques have led to the discovery of thousands of non-coding transcripts with unknown function. There are several types of non-coding linear RNAs such as microRNAs (miRNA) and long non-coding RNAs (lncRNA), as well as circular RNAs (circRNA) consisting of a closed continuous loop. This review guides the reader through important aspects of non-coding RNA biology. This includes their biogenesis, mode of actions, physiological function, as well as their role in the disease context (such as in cancer or the cardiovascular system). We specifically focus on non-coding RNAs as potential therapeutic targets and diagnostic biomarkers. PMID:27535639

  5. Bistability in self-activating genes regulated by non-coding RNAs

    NASA Astrophysics Data System (ADS)

    Miro-Bueno, Jesus

    2015-01-01

    Non-coding RNA molecules are able to regulate gene expression and play an essential role in cells. On the other hand, bistability is an important behaviour of genetic networks. Here, we propose and study an ODE model in order to show how non-coding RNA can produce bistability in a simple way. The model comprises a single gene with positive feedback that is repressed by non-coding RNA molecules. We show how the values of all the reaction rates involved in the model are able to control the transitions between the high and low states. This new model can be interesting to clarify the role of non-coding RNA molecules in genetic networks. As well, these results can be interesting in synthetic biology for developing new genetic memories and biomolecular devices based on non-coding RNAs.

  6. Long non-coding RNAs as emerging regulators of differentiation, development, and disease

    PubMed Central

    Dey, Bijan K; Mueller, Adam C; Dutta, Anindya

    2014-01-01

    A significant portion of the mammalian genome encodes numerous transcripts that are not translated into proteins, termed long non-coding RNAs. Initial studies identifying long non-coding RNAs inferred these RNA sequences were a consequence of transcriptional noise or promiscuous RNA polymerase II activity. However, the last decade has seen a revolution in the understanding of regulation and function of long non-coding RNAs. Now it has become apparent that long non-coding RNAs play critical roles in a wide variety of biological processes. In this review, we describe the current understanding of long non-coding RNA-mediated regulation of cellular processes: differentiation, development, and disease. PMID:25483404

  7. Identification and analysis of mouse non-coding RNA using transcriptome data.

    PubMed

    Zhao, Yuhui; Liu, Wanfei; Zeng, Jingyao; Liu, Shoucheng; Tan, Xinyu; Aljohi, Hasanawad; Hu, Songnian

    2016-06-01

    Transcripts are expressed spatially and temporally and they are very complicated, precise and specific; however, most studies are focused on protein-coding related genes. Recently, massively parallel cDNA sequencing (RNA-seq) has emerged to be a new and promising tool for transcriptome research, and numbers of non-coding RNAs, especially lincRNAs, have been widely identified and well characterized as important regulators of diverse biological processes. In this study, we used ultra-deep RNA-seq data from 15 mouse tissues to study the diversity and dynamic of non-coding RNAs in mouse. Using our own criteria, we identified totally 16,249 non-coding genes (21,569 non-coding RNAs) in mouse. We annotated these non-coding RNAs by diverse properties and found non-coding RNAs are generally shorter, have fewer exons, express in lower level and are more strikingly tissue-specific compared with protein-coding genes. Moreover, these non-coding RNAs show significant enrichment with transcriptional initiation and elongation signals including histone modifications (H3K4me3, H3K27me3 and H3K36me3), RNAPII binding sites and CAGE tags. The gene set enrichment analysis (GSEA) result revealed several sets of lincRNAs associated with diverse biological processes such as immune effector process, muscle development and sexual reproduction. Taken together, this study provides a more comprehensive annotation of mouse non-coding RNAs and gives an opportunity for future functional and evolutionary study of mouse non-coding RNAs. PMID:26944582

  8. Water/carbonate stripping for CO.sub.2 capture adsorber regeneration and CO.sub.2 delivery to photoautotrophs

    DOEpatents

    Chance, Ronald; Koros, William J.; McCool, Benjamin; Noel, James

    2015-08-11

    The invention provides systems and methods for the delivery of carbon to photoautotrophs. The invention utilizes low energy regeneration of adsorbent for CO.sub.2 capture and provides for effective CO.sub.2 loading into liquids useful for photoautotroph growth and/or production of photosynthetic products, such as biofuels, via photoautotrophic culture media. The inventive system comprises a fluid/membrane/fluid contactor that provides selective transfer of molecular CO.sub.2 via a dense (non-porous) membrane from a carbonate-based CO.sub.2 snipping solution to a culture medium where the CO.sub.2 is consumed by a photoautotroph for the production of biofuels, biofuel precursors or other commercial products.

  9. CncRNAs: RNAs with both coding and non-coding roles in development.

    PubMed

    Sampath, Karuna; Ephrussi, Anne

    2016-04-15

    RNAs are known to regulate diverse biological processes, either as protein-encoding molecules or as non-coding RNAs. However, a third class that comprises RNAs endowed with both protein coding and non-coding functions has recently emerged. Such bi-functional 'coding and non-coding RNAs' (cncRNAs) have been shown to play important roles in distinct developmental processes in plants and animals. Here, we discuss key examples of cncRNAs and review their roles, regulation and mechanisms of action during development. PMID:27095489

  10. The Clinical Relevance of Long Non-Coding RNAs in Cancer

    PubMed Central

    Silva, Andreia; Bullock, Marc; Calin, George

    2015-01-01

    Non-coding RNAs have long been associated with cancer development and progression, and since their earliest discovery, their clinical potential in identifying and characterizing the disease has been pursued. Long non-coding (lncRNAs), a diverse class of RNA transcripts >200 nucleotides in length with limited protein coding potential, has been only modestly studied relative to other categories of non-coding RNAs. However, recent data suggests they too may be important players in cancer. In this article, we consider the value of lncRNAs in the clinical setting, and in particular their potential roles as diagnostic and prognostic markers in cancer. Furthermore, we summarize the most significant studies linking lncRNA expression in human biological samples to cancer outcomes. The diagnostic sensitivity, specificity and validity of these non-coding RNA transcripts is compared in the various biological compartments in which they have been detected including tumor tissue, whole body fluids and exosomes. PMID:26516918

  11. [Role of long non-coding RNA in diabetes mellitus and its complications].

    PubMed

    Li, Ailing; Zhang, Zheng

    2016-03-01

    Long non-coding RNA was initially identified as "noises" of gene transcriptions. However, with the developing researches of ENCODE, it was found that the long non-coding RNAs can regulate the genomic expressions in the form of RNAs in epigenetic, transcription, and post transcriptional levels, which is involved in the regulation of diverse cellular processes and has significant influences on occurrence and precaution of human diseases. This paper introduces functions and features of the long non-coding RNAs, and sums up the internal relation between long non-coding RNAs, diabetes and diabetic complications on the basis of existing researches. These advances can provide the basis for the further understanding of molecular medicine on occurrence and evolution of diabetes. PMID:27349111

  12. Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts.

    PubMed

    Sun, Liang; Luo, Haitao; Bu, Dechao; Zhao, Guoguang; Yu, Kuntao; Zhang, Changhai; Liu, Yuanning; Chen, Runsheng; Zhao, Yi

    2013-09-01

    It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, Coding-Non-Coding Index (CNCI), by profiling adjoining nucleotide triplets to effectively distinguish protein-coding and non-coding sequences independent of known annotations. CNCI is effective for classifying incomplete transcripts and sense-antisense pairs. The implementation of CNCI offered highly accurate classification of transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, that demonstrated gene evolutionary divergence between vertebrates, and invertebrates, or between plants, and provided a long non-coding RNA catalog of orangutan. CNCI software is available at http://www.bioinfo.org/software/cnci. PMID:23892401

  13. Non-Coding RNAs as Therapeutic Targets in Hepatocellular Cancer

    PubMed Central

    Braconi, Chiara; Patel, Tushar

    2014-01-01

    Hepatocellular carcinoma (HCC) is a common malignancy that affects a large number of patients worldwide, with an increasing incidence in the United States and Europe. The therapies that are currently available for patients with inoperable HCC have limited benefits. Although molecular targeted therapies against selected cell signaling pathways have shown some promising results, their impact has been minimal. There is a need to identify and explore other targets for the development of novel therapeutics. Several non-protein coding RNAs (ncRNA) have recently been implicated in hepatocarcinogenesis and tumor progression. These ncRNA genes represent promising targets for cancer. However, therapeutic targeting of ncRNA genes has not been employed for HCC. The use of antisense oligonucleotides and viral vector delivery approaches has been shown to be feasible approaches to modulate ncRNA expression. HCC is an optimal cancer to evaluate novel RNA based therapeutic approaches because of the potential of effective delivery and uptake of therapeutic agents to the liver. In this review, we discuss selected ncRNA that could function as potential targets in HCC treatment and outline approaches to target ncRNA expression. Future challenges include the need to achieve site-specific targeting with acceptable safety and efficacy. PMID:22873215

  14. Non-coding RNAs as therapeutic targets in hepatocellular cancer.

    PubMed

    Braconi, Chiara; Patel, Tushar

    2012-11-01

    Hepatocellular carcinoma (HCC) is a common malignancy that affects a large number of patients worldwide, with an increasing incidence in the United States and Europe. The therapies that are currently available for patients with inoperable HCC have limited benefits. Although molecular targeted therapies against selected cell signaling pathways have shown some promising results, their impact has been minimal. There is a need to identify and explore other targets for the development of novel therapeutics. Several non-protein coding RNAs (ncRNA) have recently been implicated in hepatocarcinogenesis and tumor progression. These ncRNA genes represent promising targets for cancer. However, therapeutic targeting of ncRNA genes has not been employed for HCC. The use of antisense oligonucleotides and viral vector delivery approaches have been shown to be feasible approaches to modulate ncRNA expression. HCC is an optimal cancer to evaluate novel RNA based therapeutic approaches because of the potential of effective delivery and uptake of therapeutic agents to the liver. In this review, we discuss selected ncRNA that could function as potential targets in HCC treatment and outline approaches to target ncRNA expression. Future challenges include the need to achieve site-specific targeting with acceptable safety and efficacy. PMID:22873215

  15. Non-coding RNAs as emerging molecular targets of gallbladder cancer.

    PubMed

    Tekcham, Dinesh Singh; Tiwari, Pramod Kumar

    2016-08-15

    Gallbladder cancer is one of the most common cancers of biliary tract with aggressive pathophysiology, now emerging as a global health issue. Although minority of gallbladder cancer patients could receive such curative resection due to late diagnosis, this increases the survival rate. Lack of potential target molecule (s) for early diagnosis, better prognosis and effective therapy of gallbladder cancer has triggered investigators to look for novel technological or high throughput approaches to identify potential biomarker for gallbladder cancer. Intervention of non-coding RNAs in gallbladder cancer has been revealed recently. Non-coding RNAs are now widely implicated in cancer. Recent reports have revealed association of non-coding RNAs (microRNAs or miRNAs and long non-coding RNAs or lncRNAs) with gallbladder cancer. Here, we present an updated overview on the biogenesis, mechanism of action, role of non-coding RNAs, the identified cellular functions in gallbladder tumorigenesis, their prognostic & therapeutic potentials (efficacies) and future significance in developing effective biomarker(s), in future, for gallbladder. PMID:27131889

  16. Impact of Nutrition on Non-Coding RNA Epigenetics in Breast and Gynecological Cancer

    PubMed Central

    Krakowsky, Rosanna H. E.; Tollefsbol, Trygve O.

    2015-01-01

    Cancer is the second leading cause of death in females. According to the American Cancer Society, there are 327,660 new cases in breast and gynecological cancers estimated in 2014, placing emphasis on the need for cancer prevention and new cancer treatment strategies. One important approach to cancer prevention involves phytochemicals, biologically active compounds derived from plants. A variety of studies on the impact of dietary compounds found in cruciferous vegetables, green tea, and spices like curry and black pepper have revealed epigenetic changes in female cancers. Thus, an important emerging topic comprises epigenetic changes due to the modulation of non-coding RNA levels. Since it has been shown that non-coding RNAs such as microRNAs and long non-coding RNAs are aberrantly expressed in cancer, and furthermore are linked to distinct cancer phenotypes, understanding the effects of dietary compounds and supplements on the epigenetic modulator non-coding RNA is of great interest. This article reviews the current findings on nutrition-induced changes in breast and gynecological cancers at the non-coding RNA level. PMID:26075205

  17. A Micropeptide Encoded by a Putative Long Non-coding RNA Regulates Muscle Performance

    PubMed Central

    Anderson, Douglas M.; Anderson, Kelly M.; Chang, Chi-Lun; Makarewich, Catherine A.; Nelson, Benjamin R.; McAnally, John R.; Kasaragod, Prasad; Shelton, John M.; Liou, Jen; Bassel-Duby, Rhonda; Olson, Eric N.

    2015-01-01

    Summary Functional micropeptides can be concealed within RNAs that appear to be non-coding. We discovered a conserved micropeptide, that we named myoregulin (MLN), encoded by a skeletal muscle-specific RNA annotated as a putative long non-coding RNA. MLN shares structural and functional similarity with phospholamban (PLN) and sarcolipin (SLN), which inhibit SERCA, the membrane pump that controls muscle relaxation by regulating Ca2+ uptake into the sarcoplasmic reticulum (SR). MLN interacts directly with SERCA and impedes Ca2+ uptake into the SR. In contrast to PLN and SLN, which are expressed in cardiac and slow skeletal muscle in mice, MLN is robustly expressed in all skeletal muscle. Genetic deletion of MLN in mice enhances Ca2+ handling in skeletal muscle and improves exercise performance. These findings identify MLN as an important regulator of skeletal muscle physiology and highlight the possibility that additional micropeptides are encoded in the many RNAs currently annotated as non-coding. PMID:25640239

  18. Structure based approaches for targeting non-coding RNAs with small molecules

    PubMed Central

    Shortridge, Matthew D.; Varani, Gabriele

    2015-01-01

    The increasing appreciation of the central role of non-coding RNAs (miRNAs and long non coding RNAs) in chronic and degenerative human disease makes them attractive therapeutic targets. This would not be unprecedented: the bacterial ribosomal RNA is a mainstay for antibacterial treatment, while the conservation and functional importance of viral RNA regulatory elements has long suggested they would constitute attractive targets for new antivirals. Oligonucleotide-based chemistry has obvious appeals but also considerable pharmacological limitations that are yet to be addressed satisfactorily. Recent studies identifying small molecules targeting non-coding RNAs may provide an alternative approach to oligonucleotide methods. Here we review recent work investigating new structural and chemical principles for targeting RNA with small molecules. PMID:25687935

  19. The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring.

    PubMed

    Kunej, Tanja; Obsteter, Jana; Pogacar, Ziva; Horvat, Simon; Calin, George Adrian

    2014-12-01

    Long non-coding RNAs (lncRNAs) are transcripts without protein-coding capacity; initially regarded as "transcriptional noise", lately they have emerged as essential factors in both cell biology and mechanisms of disease. In this article, we present basic knowledge of lncRNA molecular mechanisms, associated physiological processes and cancer association, as well as their diagnostic and therapeutic value in the form of a decalog: (1) Non-coding RNAs (ncRNAs) are transcripts without protein-coding capacity divided by size (short and long ncRNAs), function (housekeeping RNA and regulatory RNA) and direction of transcription (sense/antisense, bidirectional, intronic and intergenic), containing a broad range of molecules with diverse properties and functions, such as messenger RNA, transfer RNA, microRNA and long non-coding RNAs. (2) Long non-coding RNAs are implicated in many molecular mechanisms, such as transcriptional regulation, post-transcriptional regulation and processing of other short ncRNAs. (3) Long non-coding RNAs play an important role in many physiological processes such as X-chromosome inactivation, cell differentiation, immune response and apoptosis. (4) Long non-coding RNAs have been linked to hallmarks of cancer: (a) sustaining proliferative signaling; (b) evading growth suppressors; (c) enabling replicative immortality; (d) activating invasion and metastasis; (e) inducing angiogenesis; (f) resisting cell death; and (g) reprogramming energy metabolism. (5) Regarding their impact on cancer cells, lncRNAs are divided into two groups: oncogenic and tumor-suppressor lncRNAs. (6) Studies of lncRNA involvement in cancer usually analyze deregulated expression patterns at the RNA level as well as the effects of single nucleotide polymorphisms and copy number variations at the DNA level. (7) Long non-coding RNAs have potential as novel biomarkers due to tissue-specific expression patterns, efficient detection in body fluids and high stability. (8) LncRNAs serve

  20. The role of long non-coding RNAs in genome formatting and expression

    PubMed Central

    Angrand, Pierre-Olivier; Vennin, Constance; Le Bourhis, Xuefen; Adriaenssens, Eric

    2015-01-01

    Long non-coding RNAs (lncRNAs) are transcripts without protein-coding potential but having a pivotal role in numerous biological functions. Long non-coding RNAs act as regulators at different levels of gene expression including chromatin organization, transcriptional regulation, and post-transcriptional control. Misregulation of lncRNAs expression has been found to be associated to cancer and other human disorders. Here, we review the different types of lncRNAs, their mechanisms of action on genome formatting and expression and emphasized on the multifaceted action of the H19 lncRNA. PMID:25972893

  1. RNA-Seq analysis provides insights for understanding photoautotrophic polyhydroxyalkanoate production in recombinant Synechocystis Sp.

    PubMed

    Lau, Nyok-Sean; Foong, Choon Pin; Kurihara, Yukio; Sudesh, Kumar; Matsui, Minami

    2014-01-01

    The photosynthetic cyanobacterium, Synechocystis sp. strain 6803, is a potential platform for the production of various chemicals and biofuels. In this study, direct photosynthetic production of a biopolymer, polyhydroxyalkanoate (PHA), in genetically engineered Synechocystis sp. achieved as high as 14 wt%. This is the highest production reported in Synechocystis sp. under photoautotrophic cultivation conditions without the addition of a carbon source. The addition of acetate increased PHA accumulation to 41 wt%, and this value is comparable to the highest production obtained with cyanobacteria. Transcriptome analysis by RNA-seq coupled with real-time PCR was performed to understand the global changes in transcript levels of cells subjected to conditions suitable for photoautotrophic PHA biosynthesis. There was lower expression of most PHA synthesis-related genes in recombinant Synechocystis sp. with higher PHA accumulation suggesting that the concentration of these enzymes is not the limiting factor to achieving high PHA accumulation. In order to cope with the higher PHA production, cells may utilize enhanced photosynthesis to drive the product formation. Results from this study suggest that the total flux of carbon is the possible driving force for the biosynthesis of PHA and the polymerizing enzyme, PHA synthase, is not the only critical factor affecting PHA-synthesis. Knowledge of the regulation or control points of the biopolymer production pathways will facilitate the further use of cyanobacteria for biotechnological applications. PMID:24466058

  2. Light Stress and Oxidative Cell Damage in Photoautotrophic Cell Suspension of Euphorbia characias L.

    PubMed Central

    Bladier, C.; Carrier, P.; Chagvardieff, P.

    1994-01-01

    A photoautotrophic cell-suspension culture of Euphorbia characias L. grown at 70 [mu]mol photons m-2 s-1 was very sensitive to light stress: the gross photosynthesis measured by using a mass spectrometric 16O2/18O2 isotope technique showed a fast decrease at a rather low light intensity of 100 [mu]mol photons m-2 s-1, far below the photosynthetic saturation level. The contribution of activated oxygen species on photosystem II photoinhibition was examined for a given light intensity. A protective effect on gross photosynthesis was observed with 1% oxygen. When light stress was applied to a methyl viologen-adapted cell suspension, photoinhibition was reduced. When 50 [mu]mol L-1 methyl viologen was added, photoinhibition was slightly enhanced. These responses suggested an involvement of superoxide radicals in the photoinhibition process of E. characias photoautotrophic cells. The long-term (16 h) effects of photoinhibition were then studied. Aldehyde (malondialdehyde and 4-hydroxyalcenals) production resulting from lipid peroxidation was stimulated in long-term stressed cells. When 50 [mu]mol L-1 methyl viologen were added, increased aldehyde production was measured. Under 1% oxygen, the aldehyde production was comparable to that of nonstressed cells. The relationship among lipid peroxidation, light intensity, and net photosynthesis suggests that aldehyde production may result from cell death provoked by a prolonged energy deficit due to the inhibition of photosynthesis. PMID:12232375

  3. [Support vector data description for finding non-coding RNA gene].

    PubMed

    Zhao, Yingjie; Wang, Zhengzhi

    2010-08-01

    In the field of computational molecule biology, there is still a challenging question of how to detect non-coding RNA gene in lots of unlabeled sequences. Generally, the methods of machine learning and classification are employed to answer this question. However, only a limited number of positive training samples and unlabeled samples are available. The negative samples are difficult to define appropriately, yet they are necessary for usual learning-then-classification method. The common way for most of the existing non-coding RNA gene finding methods is to produce a number of random sequences as negative samples, which may hold some characteristic of positive sample sequences. Consequently, the contrived uncertain factor was introduced and the performance of methods was not good enough. In this paper, Support Vector Data Description (SVDD) is in use for to learning and classification as well as for detecting non-coding RNA gene in lots of unlabeled sequences, and the k-means clustering algorithm is employed before SVDD training to deal with the high flase positive fault in the result of SVDD. The training samples (target samples) are non-coding RNA genes validated by experiment. Moreover, appropriate features were constructed by Principal Component Analysis (PCA). The effectiveness and performance of the method are demonstrated by testing the cases in NONCODE databases and E. coli genome. PMID:20842844

  4. Detecting and Comparing Non-Coding RNAs in the High-Throughput Era

    PubMed Central

    Bussotti, Giovanni; Notredame, Cedric; Enright, Anton J.

    2013-01-01

    In recent years there has been a growing interest in the field of non-coding RNA. This surge is a direct consequence of the discovery of a huge number of new non-coding genes and of the finding that many of these transcripts are involved in key cellular functions. In this context, accurately detecting and comparing RNA sequences has become important. Aligning nucleotide sequences is a key requisite when searching for homologous genes. Accurate alignments reveal evolutionary relationships, conserved regions and more generally any biologically relevant pattern. Comparing RNA molecules is, however, a challenging task. The nucleotide alphabet is simpler and therefore less informative than that of amino-acids. Moreover for many non-coding RNAs, evolution is likely to be mostly constrained at the structural level and not at the sequence level. This results in very poor sequence conservation impeding comparison of these molecules. These difficulties define a context where new methods are urgently needed in order to exploit experimental results to their full potential. This review focuses on the comparative genomics of non-coding RNAs in the context of new sequencing technologies and especially dealing with two extremely important and timely research aspects: the development of new methods to align RNAs and the analysis of high-throughput data. PMID:23887659

  5. cncRNAs: Bi-functional RNAs with protein coding and non-coding functions

    PubMed Central

    Kumari, Pooja; Sampath, Karuna

    2015-01-01

    For many decades, the major function of mRNA was thought to be to provide protein-coding information embedded in the genome. The advent of high-throughput sequencing has led to the discovery of pervasive transcription of eukaryotic genomes and opened the world of RNA-mediated gene regulation. Many regulatory RNAs have been found to be incapable of protein coding and are hence termed as non-coding RNAs (ncRNAs). However, studies in recent years have shown that several previously annotated non-coding RNAs have the potential to encode proteins, and conversely, some coding RNAs have regulatory functions independent of the protein they encode. Such bi-functional RNAs, with both protein coding and non-coding functions, which we term as ‘cncRNAs’, have emerged as new players in cellular systems. Here, we describe the functions of some cncRNAs identified from bacteria to humans. Because the functions of many RNAs across genomes remains unclear, we propose that RNAs be classified as coding, non-coding or both only after careful analysis of their functions. PMID:26498036

  6. Identification and characterization of long non-coding RNAs in rainbow trout eggs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long non-coding RNAs (lncRNAs) are in general considered as a diverse class of transcripts longer than 200 nucleotides that structurally resemble mRNAs but do not encode proteins. Recent advances in RNA sequencing (RNA-Seq) and bioinformatics methods have provided an opportunity to indentify and ana...

  7. Conservation and dissipation of light energy in desiccation-tolerant photoautotrophs, two sides of the same coin.

    PubMed

    Heber, Ulrich

    2012-09-01

    Conservation of light energy in photosynthesis is possible only in hydrated photoautotrophs. It requires complex biochemistry and is limited in capacity. Charge separation in reaction centres of photosystem II initiates energy conservation but opens also the path to photooxidative damage. A main mechanism of photoprotection active in hydrated photoautotrophs is controlled by light. This is achieved by coupling light flux to the protonation of a special thylakoid protein which activates thermal energy dissipation. This mechanism facilitates the simultaneous occurrence of energy conservation and energy dissipation but cannot completely prevent damage by light. Continuous metabolic repair is required to compensate damage. More efficient photoprotection is needed by desiccation-tolerant photoautotrophs. Loss of water during desiccation activates ultra-fast energy dissipation in mosses and lichens. Desiccation-induced energy dissipation neither requires a protonation reaction nor light but photoprotection often increases when light is present during desiccation. Two different mechanisms contribute to photoprotection of desiccated photoautotrophs. One facilitates energy dissipation in the antenna of photosystem II which is faster than energy capture by functional reaction centres. When this is insufficient for full photoprotection, the other one permits energy dissipation in the reaction centres themselves. PMID:22527974

  8. Live Cell Chemical Profiling of Temporal Redox Dynamics in a Photoautotrophic Cyanobacterium

    SciTech Connect

    Sadler, Natalie C.; Melnicki, Matthew R.; Serres, Margrethe H.; Merkley, Eric D.; Chrisler, William B.; Hill, Eric A.; Romine, Margaret F.; Kim, Sangtae; Zink, Erika M.; Datta, Suchitra; Smith, Richard D.; Beliaev, Alex S.; Konopka, Allan; Wright, Aaron T.

    2014-01-01

    Protein reduction-oxidation (redox) modification is an important mechanism that allows microorganisms to sense environmental changes and initiate cellular responses. We have developed a quantitative chemical probe approach for live cell labeling of proteins that are sensitive to redox modifications. We utilize this in vivo strategy to identify 176 proteins undergoing ~5-10 fold dynamic redox change in response to nutrient limitation and subsequent replenishment in the photoautotrophic cyanobacterium, Synechococcus sp. PCC 7002. We detect redox changes in as little as 30 seconds after nutrient perturbation, and oscillations in reduction and oxidation for 60 minutes following the perturbation. Many of the proteins undergoing dynamic redox transformations participate in the major components for the production (photosystems and electron transport chains) or consumption (Calvin-Benson cycle and protein synthesis) of reductant and/or energy in photosynthetic organisms. Thus, our in vivo approach reveals new redox-susceptible proteins, in addition to validating those previously identified in vitro.

  9. Improving a Synechocystis-based photoautotrophic chassis through systematic genome mapping and validation of neutral sites.

    PubMed

    Pinto, Filipe; Pacheco, Catarina C; Oliveira, Paulo; Montagud, Arnau; Landels, Andrew; Couto, Narciso; Wright, Phillip C; Urchueguía, Javier F; Tamagnini, Paula

    2015-12-01

    The use of microorganisms as cell factories frequently requires extensive molecular manipulation. Therefore, the identification of genomic neutral sites for the stable integration of ectopic DNA is required to ensure a successful outcome. Here we describe the genome mapping and validation of five neutral sites in the chromosome of Synechocystis sp. PCC 6803, foreseeing the use of this cyanobacterium as a photoautotrophic chassis. To evaluate the neutrality of these loci, insertion/deletion mutants were produced, and to assess their functionality, a synthetic green fluorescent reporter module was introduced. The constructed integrative vectors include a BioBrick-compatible multiple cloning site insulated by transcription terminators, constituting robust cloning interfaces for synthetic biology approaches. Moreover, Synechocystis mutants (chassis) ready to receive purpose-built synthetic modules/circuits are also available. This work presents a systematic approach to map and validate chromosomal neutral sites in cyanobacteria, and that can be extended to other organisms. PMID:26490728

  10. Screening and characterization of oleaginous Chlorella strains and exploration of photoautotrophic Chlorella protothecoides for oil production.

    PubMed

    Sun, Zheng; Zhou, Zhi-gang; Gerken, Henri; Chen, Feng; Liu, Jin

    2015-05-01

    The growth and oil production of nine Chlorella strains were comparatively assessed and Chlorellaprotothecoides CS-41 demonstrated the greatest lipid production potential. The effects of different nitrogen forms and concentrations, phosphorus concentrations and light intensities on growth and oil production were studied in laboratory columns. C. protothecoides CS-41 accumulated lipids up to 55% of dry weight, with triacylglycerol and oleic acid being 71% of total lipids and 59% of total fatty acids, respectively. High biomass and lipid productivities were achieved in outdoor panel PBRs, up to 1.25 and 0.59 g L(-1) day(-1), or 44. 1 and 16.1 g m(-2) day(-1), respectively. A two-stage cultivation strategy was proposed to enhance the algal biomass and lipid production. This is the first comprehensive investigation of both indoor and outdoor photoautotrophic C. protothecoides cultures for oil production, and C. protothecoides CS-41 represents a promising biofuel feedstock worthy of further exploration. PMID:25266686

  11. Improving a Synechocystis-based photoautotrophic chassis through systematic genome mapping and validation of neutral sites

    PubMed Central

    Pinto, Filipe; Pacheco, Catarina C.; Oliveira, Paulo; Montagud, Arnau; Landels, Andrew; Couto, Narciso; Wright, Phillip C.; Urchueguía, Javier F.; Tamagnini, Paula

    2015-01-01

    The use of microorganisms as cell factories frequently requires extensive molecular manipulation. Therefore, the identification of genomic neutral sites for the stable integration of ectopic DNA is required to ensure a successful outcome. Here we describe the genome mapping and validation of five neutral sites in the chromosome of Synechocystis sp. PCC 6803, foreseeing the use of this cyanobacterium as a photoautotrophic chassis. To evaluate the neutrality of these loci, insertion/deletion mutants were produced, and to assess their functionality, a synthetic green fluorescent reporter module was introduced. The constructed integrative vectors include a BioBrick-compatible multiple cloning site insulated by transcription terminators, constituting robust cloning interfaces for synthetic biology approaches. Moreover, Synechocystis mutants (chassis) ready to receive purpose-built synthetic modules/circuits are also available. This work presents a systematic approach to map and validate chromosomal neutral sites in cyanobacteria, and that can be extended to other organisms. PMID:26490728

  12. Enhanced lipid accumulation of photoautotrophic microalgae by high-dose CO2 mimics a heterotrophic characterization.

    PubMed

    Sun, Zhilan; Dou, Xiao; Wu, Jun; He, Bing; Wang, Yuancong; Chen, Yi-Feng

    2016-01-01

    Microalgae possess higher photosynthetic efficiency and accumulate more neutral lipids when supplied with high-dose CO2. However, the nature of lipid accumulation under conditions of elevated CO2 has not been fully elucidated so far. We now revealed that the enhanced lipid accumulation of Chlorella in high-dose CO2 was as efficient as under heterotrophic conditions and this may be attributed to the driving of enlarged carbon source. Both photoautotrophic and heterotrophic cultures were established by using Chlorella sorokiniana CS-1. A series of changes in the carbon fixation, lipid accumulation, energy conversion, and carbon-lipid conversion under high-dose CO2 (1-10%) treatment were characterized subsequently. The daily carbon fixation rate of C. sorokiniana LS-2 in 10% CO2 aeration was significantly increased compared with air CO2. Correspondingly, double oil content (28%) was observed in 10% CO2 aeration, close to 32.3% produced under heterotrophic conditions. In addition, with 10% CO2 aeration, the overall energy yield (Ψ) in Chlorella reached 12.4 from 7.3% (with air aeration) because of the enhanced daily carbon fixation rates. This treatment also improved the energetic lipid yield (Ylipid/Es) with 4.7-fold, tending to the heterotrophic parameters. More significantly, 2.2 times of carbon-lipid conversion efficiency (ηClipid/Ctotal, 42.4%) was observed in 10% CO2 aeration, towards to 53.7% in heterotrophic cultures, suggesting that more fixed carbon might flow into lipid synthesis under both 10% CO2 aeration and heterotrophic conditions. Taken together, all our evidence showed that 10% CO2 may push photoautotrophic Chlorella to display heterotrophic-like efficiency at least in lipid production. It might bring us an efficient model of lipid production based on microalgal cells with high-dose CO2, which is essential to sustain biodiesel production at large scales. PMID:26712624

  13. MicroRNAs and other non-coding RNAs as targets for anticancer drug development

    PubMed Central

    Ling, Hui; Fabbri, Muller; Calin, George A.

    2015-01-01

    With the first cancer-targeted microRNA drug, MRX34, a liposome-based miR-34 mimic, entering phase I clinical trial in patients with advanced hepatocellular carcinoma in April 2013, miRNA therapeutics are attracting special attention from both academia and biotechnology companies. Although to date the most studied non-coding RNAs (ncRNAs) are miRNAs, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognized. Here we summarize the roles of miRNAs and lncRNAs in cancer, with a focus on the recently identified novel mechanisms of action, and discuss the current strategies in designing ncRNA-targeting therapeutics, as well as the associated challenges. PMID:24172333

  14. Long non-coding RNA-mediated regulation of glucose homeostasis and diabetes

    PubMed Central

    Sun, Xinghui; Wong, Danny

    2016-01-01

    Long non-coding RNAs (lncRNAs) represent an important class of non-coding RNAs that plays key roles in regulating the expression of genes in health and disease. Accumulating genetic, experimental, and epidemiological studies highlight a growing list of lncRNAs that control glucose homeostasis and diabetic pathologies and complications. Through interactions with chromatin, RNA, and protein, lncRNAs modulate chromatin modification, mRNA stability, microRNA activity, and the function of proteins such as transcription factors. This review highlights emerging concepts in lncRNA-mediated control of glucose homeostasis as well as some of the challenges and therapeutic opportunities in the pathogenesis of diabetes and its complications. PMID:27335687

  15. Long non-coding RNA regulation of gene expression during differentiation.

    PubMed

    Lopez-Pajares, Vanessa

    2016-06-01

    Transcriptome analysis of mammalian genomes has revealed widespread transcription, much of which does not encode protein. Long non-coding RNAs (lncRNAs) are a subset of the non-coding transcriptome that are emerging as critical regulators of various cellular processes. Differentiation of stem and progenitor cells requires a careful execution of specific genetic programs, and recent studies have revealed that lncRNA expression contributes to specification of cell identity. LncRNAs participate in regulating differentiation at multiple levels of gene expression through various mechanisms of action. In this review, functional roles of lncRNAs in regulating cellular differentiation of blood, muscle, skin, cardiomyocytes, adipocytes, and neurons are discussed. PMID:26996975

  16. The emerging role of pseudogene expressed non-coding RNAs in cellular functions

    PubMed Central

    Groen, Jessica N.; Capraro, David; Morris, Kevin V.

    2014-01-01

    A paradigm shift is sweeping modern day molecular biology following the realisation that large amounts of “junk” DNA”, thought initially to be evolutionary remnants, may actually be functional. Several recent studies support a functional role for pseudogene-expressed non-coding RNAs in regulating their protein-coding counterparts. Several hundreds of pseudogenes have been reported as transcribed into RNA in a large variety of tissues and tumours. Most studies have focused on pseudogenes expressed in the sense direction, but some reports suggest that pseudogenes can also be transcribed as antisense RNAs (asRNAs). A few examples of key regulatory genes, such as PTEN and OCT4, have in fact been reported to be under the regulation of pseudogene-expressed asRNAs. Here, we review what are known about pseudogene expressed non-coding RNA mediated gene regulation and their roles in the control of epigenetic states. PMID:24842102

  17. Non-coding chloroplast DNA for plant molecular systematics at the infrageneric level.

    PubMed

    Böhle, U R; Hilger, H; Cerff, R; Martin, W F

    1994-01-01

    With primers constructed against highly conserved regions of tRNA genes (trnTUGU, trnLUAA and trnFGAA) in chloroplast DNA, we have amplified two different non-coding spacers and one intron from four species within the genus Echium L. (Boraginaceae) and from two confamilial outgroups. The trnTUGU-trnLUAA intergenic spacer contains a greater number of polymorphic sites than the trnLUAA intron or the trnLUAA-trnFGAA intergenic spacer. We analyzed a total of 11 kb of sequence data from this non-coding DNA. Total nucleotide divergence between Echium species is on the order of 1% for these regions, all of which possess infrageneric length polymorphisms. The latter two regions contain indels which occur only in the 14 Macaronesian Island endemic species of Echium studied and suggest that these may form a monophyletic group. PMID:7994117

  18. Regulatory networks of non-coding RNAs in brown/beige adipogenesis

    PubMed Central

    Xu, Shaohai; Chen, Peng; Sun, Lei

    2015-01-01

    BAT (brown adipose tissue) is specialized to burn fatty acids for heat generation and energy expenditure to defend against cold and obesity. Accumulating studies have demonstrated that manipulation of BAT activity through various strategies can regulate metabolic homoeostasis and lead to a healthy phenotype. Two classes of ncRNA (non-coding RNA), miRNA and lncRNA (long non-coding RNA), play crucial roles in gene regulation during tissue development and remodelling. In the present review, we summarize recent findings on regulatory role of distinct ncRNAs in brown/beige adipocytes, and discuss how these ncRNA regulatory networks contribute to brown/beige fat development, differentiation and function. We suggest that targeting ncRNAs could be an attractive approach to enhance BAT activity for protecting the body against obesity and its pathological consequences. PMID:26283634

  19. Estimation of correlations between copy-number variants in non-coding DNA.

    PubMed

    Stamoulis, Catherine

    2011-01-01

    Allelic DNA aberrations across our genome have been associated with normal human genetic heterogeneity as well as with a number of diseases and disorders. When copy-number variations (CNVs) occur in gene-coding regions, known relationships between genes may help us understand correlations between CNVs. However, a large number of these aberrations occur in non-coding, extragenic regions and their correlations may be characterized only quantitatively, e.g., probabilistically, but not functionally. Using a signal processing approach to CNV detection, we identified distributed CNVs in short, non-coding regions across chromosomes and investigated their potential correlations. We estimated predominantly local correlations between CNVs within the same chromosome, and a small number of apparently random long-distance correlations. PMID:22255599

  20. Elements and machinery of non-coding RNAs: toward their taxonomy

    PubMed Central

    Hirose, Tetsuro; Mishima, Yuichiro; Tomari, Yukihide

    2014-01-01

    Although recent transcriptome analyses have uncovered numerous non-coding RNAs (ncRNAs), their functions remain largely unknown. ncRNAs assemble with proteins and operate as ribonucleoprotein (RNP) machineries, formation of which is thought to be determined by specific fundamental elements embedded in the primary RNA transcripts. Knowledge about the relationships between RNA elements, RNP machinery, and molecular and physiological functions is critical for understanding the diverse roles of ncRNAs and may eventually allow their systematic classification or “taxonomy.” In this review, we catalog and discuss representative small and long non-coding RNA classes, focusing on their currently known (and unknown) RNA elements and RNP machineries. PMID:24731943

  1. Barcelona conference on epigenetics and cancer 2015: Coding and non-coding functions of the genome.

    PubMed

    Corujo, David; Mas, Gloria; Malinverni, Roberto; Di Croce, Luciano; Buschbeck, Marcus

    2016-01-01

    The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled "Coding and Non-Coding functions of the Genome" took place October 29-30, 2015 in Barcelona. The 2015 BCEC was the third edition of a series of annual conferences jointly organized by 5 leading research centers in Barcelona together with B-Debate, an initiative of BioCat. Luciano Di Croce from the Center for Genomic Regulation and Marcus Buschbeck from the Josep Carreras Leukemia Research Institute put together the scientific program with a particular focus on the role of non-coding RNAs in enhancer regulation, epigenetic control by Polycomb complexes, histone variants, and nuclear organization. In one and a half days, 22 talks and 56 posters were presented to an audience of 215 participants. PMID:26996885

  2. An expanding universe of the non-coding genome in cancer biology

    PubMed Central

    Xue, Bin; He, Lin

    2014-01-01

    Neoplastic transformation is caused by accumulation of genetic and epigenetic alterations that ultimately convert normal cells into tumor cells with uncontrolled proliferation and survival, unlimited replicative potential and invasive growth [Hanahan,D. et al. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646–674]. Although the majority of the cancer studies have focused on the functions of protein-coding genes, emerging evidence has started to reveal the importance of the vast non-coding genome, which constitutes more than 98% of the human genome. A number of non-coding RNAs (ncRNAs) derived from the ‘dark matter’ of the human genome exhibit cancer-specific differential expression and/or genomic alterations, and it is increasingly clear that ncRNAs, including small ncRNAs and long ncRNAs (lncRNAs), play an important role in cancer development by regulating protein-coding gene expression through diverse mechanisms. In addition to ncRNAs, nearly half of the mammalian genomes consist of transposable elements, particularly retrotransposons. Once depicted as selfish genomic parasites that propagate at the expense of host fitness, retrotransposon elements could also confer regulatory complexity to the host genomes during development and disease. Reactivation of retrotransposons in cancer, while capable of causing insertional mutagenesis and genome rearrangements to promote oncogenesis, could also alter host gene expression networks to favor tumor development. Taken together, the functional significance of non-coding genome in tumorigenesis has been previously underestimated, and diverse transcripts derived from the non-coding genome could act as integral functional components of the oncogene and tumor suppressor network. PMID:24747961

  3. New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs

    PubMed Central

    Schouten, Marijn; Buijink, M. Renate; Lucassen, Paul J.; Fitzsimons, Carlos P.

    2012-01-01

    Adult neurogenesis generates functional neurons from neural stem cells present in specific brain regions. It is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus (DG), in the hippocampus. With age, the function of the hippocampus and particularly the DG is impaired. For instance, adult neurogenesis is decreased with aging, in both proliferating and differentiation of newborn cells, while in parallel an age-associated decline in cognitive performance is often seen. Surprisingly, the synaptogenic potential of adult-born neurons is only marginally influenced by aging. Therefore, although proliferation, differentiation, and synaptogenesis of adult-born new neurons in the DG are closely related to each other, they are differentially affected by aging. In this review we discuss the crucial roles of a novel class of recently discovered modulators of gene expression, the small non-coding RNAs, in the regulation of adult neurogenesis. Multiple small non-coding RNAs are differentially expressed in the hippocampus. In particular a subgroup of the small non-coding RNAs, the microRNAs, fine-tune the progression of adult neurogenesis. This makes small non-coding RNAs appealing candidates to orchestrate the functional alterations in adult neurogenesis and cognition associated with aging. Finally, we summarize observations that link changes in circulating levels of steroid hormones with alterations in adult neurogenesis, cognitive decline, and vulnerability to psychopathology in advanced age, and discuss a potential interplay between steroid hormone receptors and microRNAs in cognitive decline in aging individuals. PMID:22363255

  4. Variation in conserved non-coding sequences on chromosome 5q andsusceptibility to asthma and atopy

    SciTech Connect

    Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng; Kurz,Thorsten; Dubchak, Inna; Frazer, Kelly A.; Ober, Carole

    2005-09-10

    Background: Evolutionarily conserved sequences likely havebiological function. Methods: To determine whether variation in conservedsequences in non-coding DNA contributes to risk for human disease, westudied six conserved non-coding elements in the Th2 cytokine cluster onhuman chromosome 5q31 in a large Hutterite pedigree and in samples ofoutbred European American and African American asthma cases and controls.Results: Among six conserved non-coding elements (>100 bp,>70percent identity; human-mouse comparison), we identified one singlenucleotide polymorphism (SNP) in each of two conserved elements and sixSNPs in the flanking regions of three conserved elements. We genotypedour samples for four of these SNPs and an additional three SNPs each inthe IL13 and IL4 genes. While there was only modest evidence forassociation with single SNPs in the Hutterite and European Americansamples (P<0.05), there were highly significant associations inEuropean Americans between asthma and haplotypes comprised of SNPs in theIL4 gene (P<0.001), including a SNP in a conserved non-codingelement. Furthermore, variation in the IL13 gene was strongly associatedwith total IgE (P = 0.00022) and allergic sensitization to mold allergens(P = 0.00076) in the Hutterites, and more modestly associated withsensitization to molds in the European Americans and African Americans (P<0.01). Conclusion: These results indicate that there is overalllittle variation in the conserved non-coding elements on 5q31, butvariation in IL4 and IL13, including possibly one SNP in a conservedelement, influence asthma and atopic phenotypes in diversepopulations.

  5. Distinct Expression of Long Non-Coding RNAs in an Alzheimer's Disease Model.

    PubMed

    Lee, Doo Young; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Park, Dong-Kyu; Yoo, Jung-Seok; Sunwoo, Jun-Sang; Byun, Jung-Ick; Shin, Jung-Won; Jeon, Daejong; Jung, Ki-Young; Kim, Manho; Lee, Sang Kun; Chu, Kon

    2015-01-01

    With the recent advancement in transcriptome-wide profiling approach, numerous non-coding transcripts previously unknown have been identified. Among the non-coding transcripts, long non-coding RNAs (lncRNAs) have received increasing attention for their capacity to modulate transcriptional regulation. Although alterations in the expressions of non-coding RNAs have been studied in Alzheimer's disease (AD), most research focused on the involvement of microRNAs, and comprehensive expression profiling of lncRNAs in AD has been lacking. In this study, microarray analysis was performed to procure the expression profile of lncRNAs dysregulated in a triple transgenic model of AD (3xTg-AD). A total of 4,622 lncRNAs were analyzed: 205 lncRNAs were significantly dysregulated in 3xTg-AD compared with control mice, and 230 lncRNAs were significantly dysregulated within 3xTg-AD in an age-dependent manner (≥2.0-fold, p < 0.05). Among these, 27 and 15 lncRNAs, respectively, had adjacent protein-coding genes whose expressions were also significantly dysregulated. A majority of these lncRNAs and their adjacent genes shared the same direction of dysregulation. For these pairs of lncRNAs and adjacent genes, significant Gene Ontology terms were DNA-dependent regulation of transcription, transcription regulator activity, and embryonic organ morphogenesis. One of the most highly upregulated lncRNAs had a 395 bp core sequence that overlapped with multiple chromosomal regions. This is the first study that comprehensively identified dysregulated lncRNAs in 3xTg-AD mice and will likely facilitate the development of therapeutics targeting lncRNAs in AD. PMID:25624420

  6. Sequence analysis of the 3' non-coding region of mouse immunoglobulin light chain messenger RNA.

    PubMed Central

    Hamlyn, P H; Gillam, S; Smith, M; Milstein, C

    1977-01-01

    Using an oligonucleotide d(pT10-C-A) as primer, cDNA has been transcribed from the 3' non-coding region of mouse immunoglobulin light chain mRNA and sequenced by a modification1 of the 'plus-minus' gel method2. The sequence obtained has partially corrected and extended a previously obtained sequence3. The new data contains an unusual sequence in which a trinucleotide is repeated seven times. Images PMID:405661

  7. Deciphering the function of non-coding RNAs in prostate cancer.

    PubMed

    Ramalho-Carvalho, João; Fromm, Bastian; Henrique, Rui; Jerónimo, Carmen

    2016-06-01

    The advent of next-generation sequencing methods is fuelling the discovery of multiple non-coding RNA transcripts with direct implication in cell biology and homeostasis. This new layer of biological regulation seems to be of particular importance in human pathogenesis, including cancer. The aberrant expression of ncRNAs is a feature of prostate cancer, as they promote tumor-suppressive or oncogenic activities, controlling multicellular events leading to carcinogenesis and tumor progression. From the small RNAs involved in the RNAi pathway to the long non-coding RNAs controlling chromatin remodeling, alternative splicing, and DNA repair, the non-coding transcriptome represents the significant majority of transcriptional output. As such, ncRNAs appear as exciting new diagnostic, prognostic, and therapeutic tools. However, additional work is required to characterize the RNA species, their functions, and their applicability to clinical practice in oncology. In this review, we summarize the most important features of ncRNA biology, emphasizing its relevance in prostate carcinogenesis and its potential for clinical applications. PMID:27221068

  8. Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo.

    PubMed

    Indrieri, Alessia; Grimaldi, Claudia; Zucchelli, Silvia; Tammaro, Roberta; Gustincich, Stefano; Franco, Brunella

    2016-01-01

    Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins. PMID:27265476

  9. Long Non-Coding RNAs as Master Regulators in Cardiovascular Diseases

    PubMed Central

    Archer, Krystal; Broskova, Zuzana; Bayoumi, Ahmed S.; Teoh, Jian-peng; Davila, Alec; Tang, Yaoliang; Su, Huabo; Kim, Il-man

    2015-01-01

    Cardiovascular disease is the leading cause of death in the United States, accounting for nearly one in every seven deaths. Over the last decade, various targeted therapeutics have been introduced, but there has been no corresponding improvement in patient survival. Since the mortality rate of cardiovascular disease has not been significantly decreased, efforts have been made to understand the link between heart disease and novel therapeutic targets such as non-coding RNAs. Among multiple non-coding RNAs, long non-coding RNA (lncRNA) has emerged as a novel therapeutic in cardiovascular medicine. LncRNAs are endogenous RNAs that contain over 200 nucleotides and regulate gene expression. Recent studies suggest critical roles of lncRNAs in modulating the initiation and progression of cardiovascular diseases. For example, aberrant lncRNA expression has been associated with the pathogenesis of ischemic heart failure. In this article, we present a synopsis of recent discoveries that link the roles and molecular interactions of lncRNAs to cardiovascular diseases. Moreover, we describe the prevalence of circulating lncRNAs and assess their potential utilities as biomarkers for diagnosis and prognosis of heart disease. PMID:26445043

  10. Exploiting the hypoxia sensitive non-coding genome for organ-specific physiologic reprogramming.

    PubMed

    Bischof, Corinne; Krishnan, Jaya

    2016-07-01

    In this review we highlight the role of non-coding RNAs in the development and progression of cardiac pathology and explore the possibility of disease-associated RNAs serving as targets for cardiac-directed therapeutics. Contextually, we focus on the role of stress-induced hypoxia as a driver of disease development and progression through activation of hypoxia inducible factor 1α (HIF1α) and explore mechanisms underlying HIFα function as an enforcer of cardiac pathology through direct transcriptional coupling with the non-coding transcriptome. In the interest of clarity, we will confine our analysis to cardiac pathology and focus on three defining features of the diseased state, namely metabolic, growth and functional reprogramming. It is the aim of this review to explore possible mechanisms through which HIF1α regulation of the non-coding transcriptome connects to spatiotemporal control of gene expression to drive establishment of the diseased state, and to propose strategies for the exploitation of these unique RNAs as targets for clinical therapy. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26851074

  11. Long non-coding RNAs-towards precision medicine in diabetic kidney disease?

    PubMed

    Panchapakesan, Usha; Pollock, Carol

    2016-09-01

    Diabetic kidney disease (DKD) is escalating and is the major cause of end stage kidney failure. There is increasing evidence to support the role of epigenetic factors and metabolic memory in linking the environmental and genetic causes of this disease. Although our understanding of this disease has improved, there has been no significant efficacious therapeutic translation in the last decade. Current sequencing technology has allowed interrogation of the human transcriptome. It is evident that although approximately 80% of the genome is transcribed, only 1-2% is read and coded into protein. The remaining non-coding RNA, historically assumed to be 'junk', is now known to have key roles in regulating gene function and orchestrate how and when coding genes are expressed. This largest subset of non-coding RNAs called long non-coding RNAs (LNCRNAs) drives epigenetic changes and has functional relevance best characterized in cancers and cardiovascular disease. This understanding, coupled with the availability and affordability of RNA sequencing, has shifted our therapeutic strategies towards genomic therapy in DKD. The role of LNCRNAs with respect to DKD is only just emerging. In this review we summarize the role of LNCRNAs in DKD and the existing antisense oligonucleotide therapy that may provide precise and targeted medicine to treat DKD in this postgenomic era. PMID:27503944

  12. Characters, functions and clinical perspectives of long non-coding RNAs.

    PubMed

    Wu, Ruifang; Su, Yuwen; Wu, Haijing; Dai, Yong; Zhao, Ming; Lu, Qianjin

    2016-06-01

    It is well established that most of the human genome and those of other mammals and plants are transcribed into RNA without protein-coding capacity, which we define as non-coding RNA. From siRNA to microRNA, whose functions and features have been well characterized, non-coding RNAs have been a popular topic in life science research over the last decade. Long non-coding RNAs (lncRNAs), however, as a novel class of transcripts, are distinguished from these other small RNAs. Recent studies have revealed a diverse population of lncRNAs with different sizes and functions across different species. These populations are expressed dynamically and act as important regulators in a variety of biological processes, especially in gene expression. Nevertheless, the functions and mechanisms of most lncRNAs remain unclear. In this review, we present recent progress in the identification of lncRNAs, their functions and molecular mechanisms, their roles in human diseases, their potential diagnostic and therapeutic applications as well as newer technologies for identifying deregulated lncRNAs in disease tissues. PMID:26885843

  13. Functional annotation of the vlinc class of non-coding RNAs using systems biology approach

    PubMed Central

    Laurent, Georges St.; Vyatkin, Yuri; Antonets, Denis; Ri, Maxim; Qi, Yao; Saik, Olga; Shtokalo, Dmitry; de Hoon, Michiel J.L.; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Arner, Erik; Forrest, Alistair R.R.; Nicolas, Estelle; McCaffrey, Timothy A.; Carninci, Piero; Hayashizaki, Yoshihide; Wahlestedt, Claes; Kapranov, Philipp

    2016-01-01

    Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology-based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlincRNAs genes likely function in cis to activate nearby genes. This effect while most pronounced in closely spaced vlincRNA–gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlincRNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non-coding RNAs. PMID:27001520

  14. Long and Short Non-Coding RNAs as Regulators of Hematopoietic Differentiation

    PubMed Central

    Morceau, Franck; Chateauvieux, Sébastien; Gaigneaux, Anthoula; Dicato, Mario; Diederich, Marc

    2013-01-01

    Genomic analyses estimated that the proportion of the genome encoding proteins corresponds to approximately 1.5%, while at least 66% are transcribed, suggesting that many non-coding DNA-regions generate non-coding RNAs (ncRNAs). The relevance of these ncRNAs in biological, physiological as well as in pathological processes increased over the last two decades with the understanding of their implication in complex regulatory networks. This review particularly focuses on the involvement of two large families of ncRNAs, namely microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of hematopoiesis. To date, miRNAs have been widely studied, leading to a wealth of data about processing, regulation and mechanisms of action and more specifically, their involvement in hematopoietic differentiation. Notably, the interaction of miRNAs with the regulatory network of transcription factors is well documented whereas roles, regulation and mechanisms of lncRNAs remain largely unexplored in hematopoiesis; this review gathers current data about lncRNAs as well as both potential and confirmed roles in normal and pathological hematopoiesis. PMID:23860209

  15. Long and short non-coding RNAs as regulators of hematopoietic differentiation.

    PubMed

    Morceau, Franck; Chateauvieux, Sébastien; Gaigneaux, Anthoula; Dicato, Mario; Diederich, Marc

    2013-01-01

    Genomic analyses estimated that the proportion of the genome encoding proteins corresponds to approximately 1.5%, while at least 66% are transcribed, suggesting that many non-coding DNA-regions generate non-coding RNAs (ncRNAs). The relevance of these ncRNAs in biological, physiological as well as in pathological processes increased over the last two decades with the understanding of their implication in complex regulatory networks. This review particularly focuses on the involvement of two large families of ncRNAs, namely microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of hematopoiesis. To date, miRNAs have been widely studied, leading to a wealth of data about processing, regulation and mechanisms of action and more specifically, their involvement in hematopoietic differentiation. Notably, the interaction of miRNAs with the regulatory network of transcription factors is well documented whereas roles, regulation and mechanisms of lncRNAs remain largely unexplored in hematopoiesis; this review gathers current data about lncRNAs as well as both potential and confirmed roles in normal and pathological hematopoiesis. PMID:23860209

  16. In silico prediction of long intergenic non-coding RNAs in sheep.

    PubMed

    Bakhtiarizadeh, Mohammad Reza; Hosseinpour, Batool; Arefnezhad, Babak; Shamabadi, Narges; Salami, Seyed Alireza

    2016-04-01

    Long non-coding RNAs (lncRNAs) are transcribed RNA molecules >200 nucleotides in length that do not encode proteins and serve as key regulators of diverse biological processes. Recently, thousands of long intergenic non-coding RNAs (lincRNAs), a type of lncRNAs, have been identified in mammalians using massive parallel large sequencing technologies. The availability of the genome sequence of sheep (Ovis aries) has allowed us genomic prediction of non-coding RNAs. This is the first study to identify lincRNAs using RNA-seq data of eight different tissues of sheep, including brain, heart, kidney, liver, lung, ovary, skin, and white adipose. A computational pipeline was employed to characterize 325 putative lincRNAs with high confidence from eight important tissues of sheep using different criteria such as GC content, exon number, gene length, co-expression analysis, stability, and tissue-specific scores. Sixty-four putative lincRNAs displayed tissues-specific expression. The highest number of tissues-specific lincRNAs was found in skin and brain. All novel lincRNAs that aligned to the human and mouse lincRNAs had conserved synteny. These closest protein-coding genes were enriched in 11 significant GO terms such as limb development, appendage development, striated muscle tissue development, and multicellular organismal development. The findings reported here have important implications for the study of sheep genome. PMID:27002388

  17. Genome-Wide Discovery of Long Non-Coding RNAs in Rainbow Trout

    PubMed Central

    Al-Tobasei, Rafet; Paneru, Bam; Salem, Mohamed

    2016-01-01

    The ENCODE project revealed that ~70% of the human genome is transcribed. While only 1–2% of the RNAs encode for proteins, the rest are non-coding RNAs. Long non-coding RNAs (lncRNAs) form a diverse class of non-coding RNAs that are longer than 200nt. Emerging evidence indicates that lncRNAs play critical roles in various cellular processes including regulation of gene expression. LncRNAs show low levels of gene expression and sequence conservation, which make their computational identification in genomes difficult. In this study, more than two billion Illumina sequence reads were mapped to the genome reference using the TopHat and Cufflinks software. Transcripts shorter than 200nt, with more than 83–100 amino acids ORF, or with significant homologies to the NCBI nr-protein database were removed. In addition, a computational pipeline was used to filter the remaining transcripts based on a protein-coding-score test. Depending on the filtering stringency conditions, between 31,195 and 54,503 lncRNAs were identified, with only 421 matching known lncRNAs in other species. A digital gene expression atlas revealed 2,935 tissue-specific and 3,269 ubiquitously-expressed lncRNAs. This study annotates the lncRNA rainbow trout genome and provides a valuable resource for functional genomics research in salmonids. PMID:26895175

  18. Post-GWAS methodologies for localisation of functional non-coding variants: ANGPTL3

    PubMed Central

    Oldoni, Federico; Palmen, Jutta; Giambartolomei, Claudia; Howard, Philip; Drenos, Fotios; Plagnol, Vincent; Humphries, Steve E.; Talmud, Philippa J.; Smith, Andrew J.P.

    2016-01-01

    Genome-wide association studies have confirmed the involvement of non-coding angiopoietin-like 3 (ANGPTL3) gene variants with coronary artery disease, levels of low-density lipoprotein cholesterol (LDL-C), triglycerides and ANGPTL3 mRNA transcript. Extensive linkage disequilibrium at the locus, however, has hindered efforts to identify the potential functional variants. Using regulatory annotations from ENCODE, combined with functional in vivo assays such as allele-specific formaldehyde-assisted isolation of regulatory elements, statistical approaches including eQTL/lipid colocalisation, and traditional in vitro methodologies including electrophoretic mobility shift assay and luciferase reporter assays, variants affecting the ANGPTL3 regulome were examined. From 253 variants associated with ANGPTL3 mRNA expression, and/or lipid traits, 46 were located within liver regulatory elements and potentially functional. One variant, rs10889352, demonstrated allele-specific effects on DNA-protein interactions, reporter gene expression and chromatin accessibility, in line with effects on LDL-C levels and expression of ANGPTL3 mRNA. The ANGPTL3 gene lies within DOCK7, although the variant is within non-coding regions outside of ANGPTL3, within DOCK7, suggesting complex long-range regulatory effects on gene expression. This study illustrates the power of combining multiple genome-wide datasets with laboratory data to localise functional non-coding variation and provides a model for analysis of regulatory variants from GWAS. PMID:26800306

  19. Post-GWAS methodologies for localisation of functional non-coding variants: ANGPTL3.

    PubMed

    Oldoni, Federico; Palmen, Jutta; Giambartolomei, Claudia; Howard, Philip; Drenos, Fotios; Plagnol, Vincent; Humphries, Steve E; Talmud, Philippa J; Smith, Andrew J P

    2016-03-01

    Genome-wide association studies have confirmed the involvement of non-coding angiopoietin-like 3 (ANGPTL3) gene variants with coronary artery disease, levels of low-density lipoprotein cholesterol (LDL-C), triglycerides and ANGPTL3 mRNA transcript. Extensive linkage disequilibrium at the locus, however, has hindered efforts to identify the potential functional variants. Using regulatory annotations from ENCODE, combined with functional in vivo assays such as allele-specific formaldehyde-assisted isolation of regulatory elements, statistical approaches including eQTL/lipid colocalisation, and traditional in vitro methodologies including electrophoretic mobility shift assay and luciferase reporter assays, variants affecting the ANGPTL3 regulome were examined. From 253 variants associated with ANGPTL3 mRNA expression, and/or lipid traits, 46 were located within liver regulatory elements and potentially functional. One variant, rs10889352, demonstrated allele-specific effects on DNA-protein interactions, reporter gene expression and chromatin accessibility, in line with effects on LDL-C levels and expression of ANGPTL3 mRNA. The ANGPTL3 gene lies within DOCK7, although the variant is within non-coding regions outside of ANGPTL3, within DOCK7, suggesting complex long-range regulatory effects on gene expression. This study illustrates the power of combining multiple genome-wide datasets with laboratory data to localise functional non-coding variation and provides a model for analysis of regulatory variants from GWAS. PMID:26800306

  20. Non-coding CK19 RNA in peripheral blood and tissue of breast cancer patients.

    PubMed

    Oloomi, Mana; Yardehnavi, Najmeh; Bouzari, Saeid; Moazzezy, Neda

    2013-01-01

    Breast carcinoma is the major cause of cancer-related death in women. The incidence of this carcinoma is rising and there are many attempts to decrease this problem. The aim of this study was detection of full-length cytokeratin 19 (CK19) mRNA, in peripheral blood and tissue of breast cancer patients in early stage of cancer. In this study, RT-PCR (reverse transcriptase-polymerase chain reaction) technique was used for detection of CK19 mRNA in peripheral blood and tissue of breast cancer patients. Primers were established to amplify the CK19 as a tumor marker. Moreover, CYFRA 21-1 subunit of CK19 protein was measured in the serum of patients. CK19 mRNA was detected and sequenced. It is shown that the most released CK19 mRNAs in blood and tissue of cancer patients are non-coding RNA. The mutated forms of mRNA are the incomplete transcripts of protein-coding gene as a long non-coding RNA (lncRNA) that could regulate gene expression. Moreover, small non-coding RNA (ncRNA) as fragments of CK19 is mostly observed in this experiment. They may play a role in tumorogenesis and their biologic exact function in breast cancer should be further elucidated. PMID:23585313

  1. Profiling Caenorhabditis elegans non-coding RNA expression with a combined microarray.

    PubMed

    He, Housheng; Cai, Lun; Skogerbø, Geir; Deng, Wei; Liu, Tao; Zhu, Xiaopeng; Wang, Yudong; Jia, Dong; Zhang, Zhihua; Tao, Yong; Zeng, Haipan; Aftab, Muhammad Nauman; Cui, Yan; Liu, Guozhen; Chen, Runsheng

    2006-01-01

    Small non-coding RNAs (ncRNAs) are encoded by genes that function at the RNA level, and several hundred ncRNAs have been identified in various organisms. Here we describe an analysis of the small non-coding transcriptome of Caenorhabditis elegans, microRNAs excepted. As a substantial fraction of the ncRNAs is located in introns of protein-coding genes in C.elegans, we also analysed the relationship between ncRNA and host gene expression. To this end, we designed a combined microarray, which included probes against ncRNA as well as host gene mRNA transcripts. The microarray revealed pronounced differences in expression profiles, even among ncRNAs with housekeeping functions (e.g. snRNAs and snoRNAs), indicating distinct developmental regulation and stage-specific functions of a number of novel transcripts. Analysis of ncRNA-host mRNA relations showed that the expression of intronic ncRNA loci with conserved upstream motifs was not correlated to (and much higher than) expression levels of their host genes. Even promoter-less intronic ncRNA loci, though showing a clear correlation to host gene expression, appeared to have a surprising amount of 'expressional freedom', depending on host gene function. Taken together, our microarray analysis presents a more complete and detailed picture of a non-coding transcriptome than hitherto has been presented for any other multicellular organism. PMID:16738136

  2. Prospective and therapeutic screening value of non-coding RNA as biomarkers in cardiovascular disease

    PubMed Central

    Busch, Albert; Eken, Suzanne M.

    2016-01-01

    Non-coding RNA (ncRNA) is a class of genetic, epigenetic and translational regulators, containing short and long transcripts with intriguing abilities for use as biomarkers due to their superordinate role in disease development. In the past five years many of these have been investigated in cardiovascular diseases (CVD), mainly myocardial infarction (MI) and heart failure. To extend this view, we summarize the existing data about ncRNA as biomarker in the whole entity of CVDs by literature-based review and comparison of the identified candidates. The myomirs miRNA-1, -133a/b, -208a, -499 with well-defined cellular functions have proven equal to classic protein biomarkers for disease detection in MI. Other microRNAs (miRNAs) were reproducibly found to correlate with disease, disease severity and outcome in heart failure, stroke, coronary artery disease (CAD) and aortic aneurysm. An additional utilization has been discovered for therapeutic monitoring. The function of long non-coding transcripts is only about to be unraveled, yet shows great potential for outcome prediction. ncRNA biomarkers have a distinct role if no alternative test is available or has is performing poorly. With increasing mechanistic understanding, circulating miRNA and long non-coding transcripts will provide useful disease information with high predictive power. PMID:27429962

  3. Functional annotation of the vlinc class of non-coding RNAs using systems biology approach.

    PubMed

    Laurent, Georges St; Vyatkin, Yuri; Antonets, Denis; Ri, Maxim; Qi, Yao; Saik, Olga; Shtokalo, Dmitry; de Hoon, Michiel J L; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Arner, Erik; Forrest, Alistair R R; Nicolas, Estelle; McCaffrey, Timothy A; Carninci, Piero; Hayashizaki, Yoshihide; Wahlestedt, Claes; Kapranov, Philipp

    2016-04-20

    Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology-based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlincRNAs genes likely function incisto activate nearby genes. This effect while most pronounced in closely spaced vlincRNA-gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlincRNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non-coding RNAs. PMID:27001520

  4. Prospective and therapeutic screening value of non-coding RNA as biomarkers in cardiovascular disease.

    PubMed

    Busch, Albert; Eken, Suzanne M; Maegdefessel, Lars

    2016-06-01

    Non-coding RNA (ncRNA) is a class of genetic, epigenetic and translational regulators, containing short and long transcripts with intriguing abilities for use as biomarkers due to their superordinate role in disease development. In the past five years many of these have been investigated in cardiovascular diseases (CVD), mainly myocardial infarction (MI) and heart failure. To extend this view, we summarize the existing data about ncRNA as biomarker in the whole entity of CVDs by literature-based review and comparison of the identified candidates. The myomirs miRNA-1, -133a/b, -208a, -499 with well-defined cellular functions have proven equal to classic protein biomarkers for disease detection in MI. Other microRNAs (miRNAs) were reproducibly found to correlate with disease, disease severity and outcome in heart failure, stroke, coronary artery disease (CAD) and aortic aneurysm. An additional utilization has been discovered for therapeutic monitoring. The function of long non-coding transcripts is only about to be unraveled, yet shows great potential for outcome prediction. ncRNA biomarkers have a distinct role if no alternative test is available or has is performing poorly. With increasing mechanistic understanding, circulating miRNA and long non-coding transcripts will provide useful disease information with high predictive power. PMID:27429962

  5. Non-coding RNAs as Emerging Regulators of Neural Injury Responses and Regeneration.

    PubMed

    Zhou, Songlin; Ding, Fei; Gu, Xiaosong

    2016-06-01

    Non-coding RNAs (ncRNAs) are a large cluster of RNAs that do not encode proteins, but have multiple functions in diverse cellular processes. Mounting evidence indicates the involvement of ncRNAs in the physiology and pathophysiology of the central and peripheral nervous systems. It has been shown that numerous ncRNAs, especially microRNAs and long non-coding RNAs, are differentially expressed after insults such as acquired brain injury, spinal cord injury, and peripheral nerve injury. These ncRNAs affect neuronal survival, neurite regrowth, and glial phenotype primarily by targeting specific mRNAs, resulting in translation repression or degradation of the mRNAs. An increasing number of studies have investigated the regulatory roles of microRNAs and long non-coding RNAs in neural injury and regeneration, and thus a new research field is emerging. In this review, we highlight current progress in the field in an attempt to provide further insight into post-transcriptional changes occurring after neural injury, and to facilitate the potential use of ncRNAs for improving neural regeneration. We also suggest potential directions for future studies. PMID:27037691

  6. Current Status of Long Non-Coding RNAs in Human Breast Cancer.

    PubMed

    Cerk, Stefanie; Schwarzenbacher, Daniela; Adiprasito, Jan Basri; Stotz, Michael; Hutterer, Georg C; Gerger, Armin; Ling, Hui; Calin, George Adrian; Pichler, Martin

    2016-01-01

    Breast cancer represents a major health burden in Europe and North America, as recently published data report breast cancer as the second leading cause of cancer related death in women worldwide. Breast cancer is regarded as a highly heterogeneous disease in terms of clinical course and biological behavior and can be divided into several molecular subtypes, with different prognosis and treatment responses. The discovery of numerous non-coding RNAs has dramatically changed our understanding of cell biology, especially the pathophysiology of cancer. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts >200 nucleotides in length. Several studies have demonstrated their role as key regulators of gene expression, cell biology and carcinogenesis. Deregulated expression levels of lncRNAs have been observed in various types of cancers including breast cancer. lncRNAs are involved in cancer initiation, progression, and metastases. In this review, we summarize the recent literature to highlight the current status of this class of long non-coding lncRNAs in breast cancer. PMID:27608009

  7. Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo

    PubMed Central

    Indrieri, Alessia; Grimaldi, Claudia; Zucchelli, Silvia; Tammaro, Roberta; Gustincich, Stefano; Franco, Brunella

    2016-01-01

    Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins. PMID:27265476

  8. Non-coding RNAs: Functions and applications in endocrine-related cancer.

    PubMed

    Venkatesh, Thejaswini; Suresh, Padmanaban S; Tsutsumi, Rie

    2015-11-15

    A significant fraction of the human genome is transcribed as non-coding RNAs (ncRNAs). This non-coding transcriptome has challenged the notion of the central dogma and its involvement in transcriptional and post-transcriptional regulation of gene expression is well established. Interestingly, several ncRNAs are dysregulated in cancer and current non-coding transcriptome research aims to use our increasing knowledge of these ncRNAs for the development of cancer biomarkers and anti-cancer drugs. In endocrine-related cancers, for which survival rates can be relatively low, there is a need for such advancements. In this review, we aimed to summarize the roles and clinical implications of recently discovered ncRNAs, including long ncRNAs, PIWI-interacting RNAs, tRNA- and Y RNA-derived ncRNAs, and small nucleolar RNAs, in endocrine-related cancers affecting both sexes. We focus on recent studies highlighting discoveries in ncRNA biology and expression in cancer, and conclude with a discussion on the challenges and future directions, including clinical application. ncRNAs show great promise as diagnostic tools and therapeutic targets, but further work is necessary to realize the potential of these unconventional transcripts. PMID:26360585

  9. NCAD, a database integrating the intrinsic conformational preferences of non-coded amino acids

    PubMed Central

    Revilla-López, Guillem; Torras, Juan; Curcó, David; Casanovas, Jordi; Calaza, M. Isabel; Zanuy, David; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Grodzinski, Piotr; Alemán, Carlos

    2010-01-01

    Peptides and proteins find an ever-increasing number of applications in the biomedical and materials engineering fields. The use of non-proteinogenic amino acids endowed with diverse physicochemical and structural features opens the possibility to design proteins and peptides with novel properties and functions. Moreover, non-proteinogenic residues are particularly useful to control the three-dimensional arrangement of peptidic chains, which is a crucial issue for most applications. However, information regarding such amino acids –also called non-coded, non-canonical or non-standard– is usually scattered among publications specialized in quite diverse fields as well as in patents. Making all these data useful to the scientific community requires new tools and a framework for their assembly and coherent organization. We have successfully compiled, organized and built a database (NCAD, Non-Coded Amino acids Database) containing information about the intrinsic conformational preferences of non-proteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, conformational propensities established experimentally, and applications. The architecture of the database is presented in this work together with the first family of non-coded residues included, namely, α-tetrasubstituted α-amino acids. Furthermore, the NCAD usefulness is demonstrated through a test-case application example. PMID:20455555

  10. A two-dimensional mutate-and-map strategy for non-coding RNA structure

    NASA Astrophysics Data System (ADS)

    Kladwang, Wipapat; Vanlang, Christopher C.; Cordero, Pablo; Das, Rhiju

    2011-12-01

    Non-coding RNAs fold into precise base-pairing patterns to carry out critical roles in genetic regulation and protein synthesis, but determining RNA structure remains difficult. Here, we show that coupling systematic mutagenesis with high-throughput chemical mapping enables accurate base-pair inference of domains from ribosomal RNA, ribozymes and riboswitches. For a six-RNA benchmark that has challenged previous chemical/computational methods, this ‘mutate-and-map’ strategy gives secondary structures that are in agreement with crystallography (helix error rates, 2%), including a blind test on a double-glycine riboswitch. Through modelling of partially ordered states, the method enables the first test of an interdomain helix-swap hypothesis for ligand-binding cooperativity in a glycine riboswitch. Finally, the data report on tertiary contacts within non-coding RNAs, and coupling to the Rosetta/FARFAR algorithm gives nucleotide-resolution three-dimensional models (helix root-mean-squared deviation, 5.7 Å) of an adenine riboswitch. These results establish a promising two-dimensional chemical strategy for inferring the secondary and tertiary structures that underlie non-coding RNA behaviour.

  11. Photoautotrophic production of D-lactic acid in an engineered cyanobacterium

    PubMed Central

    2013-01-01

    Background The world faces the challenge to develop sustainable technologies to replace thousands of products that have been generated from fossil fuels. Microbial cell factories serve as promising alternatives for the production of diverse commodity chemicals and biofuels from renewable resources. For example, polylactic acid (PLA) with its biodegradable properties is a sustainable, environmentally friendly alternative to polyethylene. At present, PLA microbial production is mainly dependent on food crops such as corn and sugarcane. Moreover, optically pure isomers of lactic acid are required for the production of PLA, where D-lactic acid controls the thermochemical and physical properties of PLA. Henceforth, production of D-lactic acid through a more sustainable source (CO2) is desirable. Results We have performed metabolic engineering on Synechocystis sp. PCC 6803 for the phototrophic synthesis of optically pure D-lactic acid from CO2. Synthesis of optically pure D-lactic acid was achieved by utilizing a recently discovered enzyme (i.e., a mutated glycerol dehydrogenase, GlyDH*). Significant improvements in D-lactic acid synthesis were achieved through codon optimization and by balancing the cofactor (NADH) availability through the heterologous expression of a soluble transhydrogenase. We have also discovered that addition of acetate to the cultures improved lactic acid production. More interestingly, 13C-pathway analysis revealed that acetate was not used for the synthesis of lactic acid, but was mainly used for synthesis of certain biomass building blocks (such as leucine and glutamate). Finally, the optimal strain was able to accumulate 1.14 g/L (photoautotrophic condition) and 2.17 g/L (phototrophic condition with acetate) of D-lactate in 24 days. Conclusions We have demonstrated the photoautotrophic production of D-lactic acid by engineering a cyanobacterium Synechocystis 6803. The engineered strain shows an excellent D-lactic acid productivity from CO2. In

  12. Mechanistic and Kinetic Differences between Reverse Transcriptases of Vpx Coding and Non-coding Lentiviruses*

    PubMed Central

    Lenzi, Gina M.; Domaoal, Robert A.; Kim, Dong-Hyun; Schinazi, Raymond F.; Kim, Baek

    2015-01-01

    Among lentiviruses, HIV Type 2 (HIV-2) and many simian immunodeficiency virus (SIV) strains replicate rapidly in non-dividing macrophages, whereas HIV Type 1 (HIV-1) replication in this cell type is kinetically delayed. The efficient replication capability of HIV-2/SIV in non-dividing cells is induced by a unique, virally encoded accessory protein, Vpx, which proteasomally degrades the host antiviral restriction factor, SAM domain- and HD domain-containing protein 1 (SAMHD1). SAMHD1 is a dNTPase and kinetically suppresses the reverse transcription step of HIV-1 in macrophages by hydrolyzing and depleting cellular dNTPs. In contrast, Vpx, which is encoded by HIV-2/SIV, kinetically accelerates reverse transcription by counteracting SAMHD1 and then elevating cellular dNTP concentration in non-dividing cells. Here, we conducted the pre-steady-state kinetic analysis of reverse transcriptases (RTs) from two Vpx non-coding and two Vpx coding lentiviruses. At all three sites of the template tested, the two RTs of the Vpx non-coding viruses (HIV-1) displayed higher kpol values than the RTs of the Vpx coding HIV-2/SIV, whereas there was no significant difference in the Kd values of these two groups of RTs. When we employed viral RNA templates that induce RT pausing by their secondary structures, the HIV-1 RTs showed more efficient DNA synthesis through pause sites than the HIV-2/SIV RTs, particularly at low dNTP concentrations found in macrophages. This kinetic study suggests that RTs of the Vpx non-coding HIV-1 may have evolved to execute a faster kpol step, which includes the conformational changes and incorporation chemistry, to counteract the limited dNTP concentration found in non-dividing cells and still promote efficient viral reverse transcription. PMID:26483545

  13. NONCODEv4: exploring the world of long non-coding RNA genes

    PubMed Central

    Xie, Chaoyong; Yuan, Jiao; Li, Hui; Li, Ming; Zhao, Guoguang; Bu, Dechao; Zhu, Weimin; Wu, Wei; Chen, Runsheng; Zhao, Yi

    2014-01-01

    NONCODE (http://www.bioinfo.org/noncode/) is an integrated knowledge database dedicated to non-coding RNAs (excluding tRNAs and rRNAs). Non-coding RNAs (ncRNAs) have been implied in diseases and identified to play important roles in various biological processes. Since NONCODE version 3.0 was released 2 years ago, discovery of novel ncRNAs has been promoted by high-throughput RNA sequencing (RNA-Seq). In this update of NONCODE, we expand the ncRNA data set by collection of newly identified ncRNAs from literature published in the last 2 years and integration of the latest version of RefSeq and Ensembl. Particularly, the number of long non-coding RNA (lncRNA) has increased sharply from 73 327 to 210 831. Owing to similar alternative splicing pattern to mRNAs, the concept of lncRNA genes was put forward to help systematic understanding of lncRNAs. The 56 018 and 46 475 lncRNA genes were generated from 95 135 and 67 628 lncRNAs for human and mouse, respectively. Additionally, we present expression profile of lncRNA genes by graphs based on public RNA-seq data for human and mouse, as well as predict functions of these lncRNA genes. The improvements brought to the database also include an incorporation of an ID conversion tool from RefSeq or Ensembl ID to NONCODE ID and a service of lncRNA identification. NONCODE is also accessible through http://www.noncode.org/. PMID:24285305

  14. Mechanistic and Kinetic Differences between Reverse Transcriptases of Vpx Coding and Non-coding Lentiviruses.

    PubMed

    Lenzi, Gina M; Domaoal, Robert A; Kim, Dong-Hyun; Schinazi, Raymond F; Kim, Baek

    2015-12-11

    Among lentiviruses, HIV Type 2 (HIV-2) and many simian immunodeficiency virus (SIV) strains replicate rapidly in non-dividing macrophages, whereas HIV Type 1 (HIV-1) replication in this cell type is kinetically delayed. The efficient replication capability of HIV-2/SIV in non-dividing cells is induced by a unique, virally encoded accessory protein, Vpx, which proteasomally degrades the host antiviral restriction factor, SAM domain- and HD domain-containing protein 1 (SAMHD1). SAMHD1 is a dNTPase and kinetically suppresses the reverse transcription step of HIV-1 in macrophages by hydrolyzing and depleting cellular dNTPs. In contrast, Vpx, which is encoded by HIV-2/SIV, kinetically accelerates reverse transcription by counteracting SAMHD1 and then elevating cellular dNTP concentration in non-dividing cells. Here, we conducted the pre-steady-state kinetic analysis of reverse transcriptases (RTs) from two Vpx non-coding and two Vpx coding lentiviruses. At all three sites of the template tested, the two RTs of the Vpx non-coding viruses (HIV-1) displayed higher kpol values than the RTs of the Vpx coding HIV-2/SIV, whereas there was no significant difference in the Kd values of these two groups of RTs. When we employed viral RNA templates that induce RT pausing by their secondary structures, the HIV-1 RTs showed more efficient DNA synthesis through pause sites than the HIV-2/SIV RTs, particularly at low dNTP concentrations found in macrophages. This kinetic study suggests that RTs of the Vpx non-coding HIV-1 may have evolved to execute a faster kpol step, which includes the conformational changes and incorporation chemistry, to counteract the limited dNTP concentration found in non-dividing cells and still promote efficient viral reverse transcription. PMID:26483545

  15. Long Intergenic Non-Coding RNAs: Novel Drivers of Human Lymphocyte Differentiation

    PubMed Central

    Panzeri, Ilaria; Rossetti, Grazisa; Abrignani, Sergio; Pagani, Massimiliano

    2015-01-01

    Upon recognition of a foreign antigen, CD4+ naïve T lymphocytes proliferate and differentiate into subsets with distinct functions. This process is fundamental for the effective immune system function, as CD4+ T cells orchestrate both the innate and adaptive immune response. Traditionally, this differentiation event has been regarded as the acquisition of an irreversible cell fate so that memory and effector CD4+ T subsets were considered terminally differentiated cells or lineages. Consequently, these lineages are conventionally defined thanks to their prototypical set of cytokines and transcription factors. However, recent findings suggest that CD4+ T lymphocytes possess a remarkable phenotypic plasticity, as they can often re-direct their functional program depending on the milieu they encounter. Therefore, new questions are now compelling such as which are the molecular determinants underlying plasticity and stability and how the balance between these two opposite forces drives the cell fate. As already mentioned, in some cases, the mere expression of cytokines and master regulators could not fully explain lymphocytes plasticity. We should consider other layers of regulation, including epigenetic factors such as the modulation of chromatin state or the transcription of non-coding RNAs, whose high cell-specificity give a hint on their involvement in cell fate determination. In this review, we will focus on the recent advances in understanding CD4+ T lymphocytes subsets specification from an epigenetic point of view. In particular, we will emphasize the emerging importance of non-coding RNAs as key players in these differentiation events. We will also present here new data from our laboratory highlighting the contribution of long non-coding RNAs in driving human CD4+ T lymphocytes differentiation. PMID:25926836

  16. Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease

    PubMed Central

    Qureshi, Irfan A.; Mehler, Mark F.

    2012-01-01

    Novel classes of small and long non-coding RNAs (ncRNAs) are being characterized at a rapid pace, driven by recent paradigm shifts in our understanding of genomic architecture, regulation and transcriptional output, as well as by innovations in sequencing technologies and computational and systems biology. These ncRNAs can interact with DNA, RNA and protein molecules; engage in diverse structural, functional and regulatory activities; and have roles in nuclear organization and transcriptional, post-transcriptional and epigenetic processes. This expanding inventory of ncRNAs is implicated in mediating a broad spectrum of processes including brain evolution, development, synaptic plasticity and disease pathogenesis. PMID:22814587

  17. TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements

    PubMed Central

    Maliszewska-Olejniczak, Kamila; Gruchota, Julita; Gromadka, Robert; Denby Wilkes, Cyril; Arnaiz, Olivier; Mathy, Nathalie; Duharcourt, Sandra; Bétermier, Mireille; Nowak, Jacek K.

    2015-01-01

    Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs) in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline) nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs). Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium, and establishes for

  18. TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements.

    PubMed

    Maliszewska-Olejniczak, Kamila; Gruchota, Julita; Gromadka, Robert; Denby Wilkes, Cyril; Arnaiz, Olivier; Mathy, Nathalie; Duharcourt, Sandra; Bétermier, Mireille; Nowak, Jacek K

    2015-07-01

    Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs) in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline) nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs). Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium, and establishes for

  19. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer

    PubMed Central

    Fang, Yiwen; Fullwood, Melissa J.

    2016-01-01

    Long non-coding RNAs (lncRNAs) play important roles in cancer. They are involved in chromatin remodeling, as well as transcriptional and post-transcriptional regulation, through a variety of chromatin-based mechanisms and via cross-talk with other RNA species. lncRNAs can function as decoys, scaffolds, and enhancer RNAs. This review summarizes the characteristics of lncRNAs, including their roles, functions, and working mechanisms, describes methods for identifying and annotating lncRNAs, and discusses future opportunities for lncRNA-based therapies using antisense oligonucleotides. PMID:26883671

  20. Non-coding functions of alternative pre-mRNA splicing in development

    PubMed Central

    Mockenhaupt, Stefan; Makeyev, Eugene V.

    2015-01-01

    A majority of messenger RNA precursors (pre-mRNAs) in the higher eukaryotes undergo alternative splicing to generate more than one mature product. By targeting the open reading frame region this process increases diversity of protein isoforms beyond the nominal coding capacity of the genome. However, alternative splicing also frequently controls output levels and spatiotemporal features of cellular and organismal gene expression programs. Here we discuss how these non-coding functions of alternative splicing contribute to development through regulation of mRNA stability, translational efficiency and cellular localization. PMID:26493705

  1. Myelin basic protein synthesis is regulated by small non-coding RNA 715.

    PubMed

    Bauer, Nina M; Moos, Christina; van Horssen, Jack; Witte, Maarten; van der Valk, Paul; Altenhein, Benjamin; Luhmann, Heiko J; White, Robin

    2012-09-01

    Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP translation. Here we identify the small non-coding RNA 715 (sncRNA715) as an inhibitor of MBP translation. SncRNA715 localizes to cytoplasmic granular structures and associates with MBP mRNA transport granule components. We also detect increased levels of sncRNA715 in demyelinated chronic human multiple sclerosis lesions, which contain MBP mRNA but lack MBP protein. PMID:22744314

  2. RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts

    PubMed Central

    Geisler, Sarah; Coller, Jeff

    2016-01-01

    The increased application of transcriptome-wide profiling approaches has led to an explosion in the number of documented long non-coding RNAs (lncRNAs). While these new and enigmatic players in the complex transcriptional milieu are encoded by a significant proportion of the genome, their functions are mostly unknown. Early discoveries support a paradigm in which lncRNAs regulate transcription via chromatin modulation, but new functions are steadily emerging. Given the biochemical versatility of RNA, lncRNAs may be used for various tasks, including post-transcriptional regulation, organization of protein complexes, cell-cell signalling and allosteric regulation of proteins. PMID:24105322

  3. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs) . Volume 2; Appendices

    NASA Technical Reports Server (NTRS)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This document contains the appendices to the main report.

  4. The Beginning of the Road for Non-Coding RNAs in Normal Hematopoiesis and Hematologic Malignancies

    PubMed Central

    Heuston, Elisabeth F.; Lemon, Kenya T.; Arceci, Robert J.

    2011-01-01

    The field of non-coding RNAs (ncRNAs) encompasses a wide array of RNA classes that are indispensible for the regulation of cellular activities. However, de-regulation of these ncRNAs can also play key roles in malignant transformation and cancer cell behavior. In this article we survey a select group of microRNAs and long ncRNAs that appear to contribute in keys ways to the development of acute and chronic leukemias, as well as contribute to their diagnosis, prognosis, and potentially, their treatment. PMID:22303388

  5. Non-coding RNAs as the bridge between epigenetic mechanisms, lineages and domains of life

    PubMed Central

    Sela, Mor; Kloog, Yoel; Rechavi, Oded

    2014-01-01

    Many cases of heritable environmental responses have been documented but the underlying mechanisms are largely unknown. Recently, inherited RNA interference has been shown to act as a multigenerational genome surveillance apparatus. We suggest that inheritance of regulatory RNAs is at the root of many other epigenetic phenomena, the trigger that induces other epigenetic mechanisms, such as the depositing of histone modifications and DNA methylation. In addition, we explore the possibility that interacting organisms influence each other's transcriptomes by exchanging heterologous non-coding RNAs. PMID:24882818

  6. Stochastic bursts in the kinetics of gene expression with regulation by long non-coding RNAs

    NASA Astrophysics Data System (ADS)

    Zhdanov, V. P.

    2010-09-01

    One of the main recent breakthroughs in cellular biology is a discovery of numerous non-coding RNAs (ncR-NAs). We outline abilities of long ncRNAs and articulate that the corresponding kinetics may frequently exhibit stochastic bursts. For example, we scrutinize one of the generic cases when the gene transcription is regulated by competitive attachment of ncRNA and protein to a regulatory site. Our Monte Carlo simulations show that in this case one can observe huge long transcriptional bursts consisting of short bursts.

  7. Multisubunit RNA Polymerases IV and V: Purveyors of Non-Coding RNA for Plant Gene Silencing

    SciTech Connect

    Haag, Jeremy R.; Pikaard, Craig S.

    2011-08-01

    In all eukaryotes, nuclear DNA-dependent RNA polymerases I, II and III synthesize the myriad RNAs that are essential for life. Remarkably, plants have evolved two additional multisubunit RNA polymerases, RNA polymerases IV and V, which orchestrate non-coding RNA-mediated gene silencing processes affecting development, transposon taming, antiviral defence and allelic crosstalk. Biochemical details concerning the templates and products of RNA polymerases IV and V are lacking. However, their subunit compositions reveal that they evolved as specialized forms of RNA polymerase II, which provides the unique opportunity to study the functional diversification of a eukaryotic RNA polymerase family.

  8. Myelin Basic Protein synthesis is regulated by small non-coding RNA 715

    PubMed Central

    Bauer, Nina M; Moos, Christina; van Horssen, Jack; Witte, Maarten; van der Valk, Paul; Altenhein, Benjamin; Luhmann, Heiko J; White, Robin

    2012-01-01

    Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP translation. Here we identify the small non-coding RNA 715 (sncRNA715) as an inhibitor of MBP translation. SncRNA715 localizes to cytoplasmic granular structures and associates with MBP mRNA transport granule components. We also detect increased levels of sncRNA715 in demyelinated chronic human multiple sclerosis lesions, which contain MBP mRNA but lack MBP protein. PMID:22744314

  9. Functional diversity of long non-coding RNAs in immune regulation

    PubMed Central

    Geng, Hua; Tan, Xiao-Di

    2016-01-01

    Precise and dynamic regulation of gene expression is a key feature of immunity. In recent years, rapid advances in transcriptome profiling analysis have led to recognize long non-coding RNAs (lncRNAs) as an additional layer of gene regulation context. In the immune system, lncRNAs are found to be widely expressed in immune cells including monocytes, macrophages, dendritic cells (DCs), neutrophils, T cells and B cells during their development, differentiation and activation. However, the functional importance of immune-related lncRNAs is just emerging to be characterized. In this review, we discuss the up-to-date knowledge of lncRNAs in immune regulation.

  10. Epigenetic modifications and long non-coding RNAs influence pancreas development and function

    PubMed Central

    Arnes, Luis; Sussel, Lori

    2015-01-01

    Insulin-producing β-cells within the pancreatic islet of Langerhans are responsible for maintaining glucose homeostasis; the loss or malfunction of β-cells results in diabetes mellitus. Recent advances in cell purification strategies and sequencing technologies as well as novel molecular tools have revealed that epigenetic modifications and long non-coding RNAs represent an integral part of the transcriptional mechanisms regulating pancreas development and β-cell function. Importantly, these findings have uncovered a new layer of gene regulation in the pancreas that can be exploited to enhance the restoration and/or repair of β-cells to treat diabetes. PMID:25812926

  11. An altered Q sub B polypeptide as the basis for atrazine resistance in photoautotrophic potato cells

    SciTech Connect

    Smeda, R.J.; Hasegawa, P.M.; Weller, S.C. )

    1990-05-01

    A photoautotrophic potato cell line (variant) was isolated and is capable of sustained growth in media containing the herbicide atrazine at concentrations up to 100-fold greater than the lethal concentration (1.0 {mu}M) for the unselected (wild type) cell line. The basis for atrazine resistance could not be identified by differential uptake or metabolism. Photosynthetic electron transport rates for both intact cell and isolated thylakoid membranes from chloroplasts were unaffected in variant cells at atrazine concentrations up to 100-fold greater than for wild type cells. Photoaffinity labeling of isolated thylakoid membranes from both cell lines with {sup 14}C-azidoatrazine revealed an altered Q{sub B} polypeptide in variant cells resulting in low or no affinity for atrazine. A portion of the chloroplast psbA gene, encoding the Q{sub B} polypeptide, was sequenced for both cell lines. The basis for atrazine resistance in variant cells was identified as a single base change resulting in the alteration of serine to threonine at position 264 of the Q{sub B} polypeptide. In addition to atrazine resistance, variant cells exhibit enhanced tolerance to the herbicides DCMU and metribuzin, but greater sensitivity to bentazon. No reductions in variant cell growth and photosynthetic efficiency in the absence of atrazine were observed.

  12. Direct membrane-carbonation photobioreactor producing photoautotrophic biomass via carbon dioxide transfer and nutrient removal.

    PubMed

    Kim, Hyun-Woo; Cheng, Jing; Rittmann, Bruce E

    2016-03-01

    An advanced-material photobioreactor, the direct membrane-carbonation photobioreactor (DMCPBR), was tested to investigate the impact of directly submerging a membrane carbonation (MC) module of hollow-fiber membranes inside the photobioreactor. Results demonstrate that the DMCPBR utilized over 90% of the supplied CO2 by matching the CO2 flux to the C demand of photoautotrophic biomass growth. The surface area of the submerged MC module was the key to control CO2 delivery and biomass productivity. Tracking the fate of supplied CO2 explained how the DMCPBR reduced loss of gaseous CO2 while matching the inorganic carbon (IC) demand to its supply. Accurate fate analysis required that the biomass-associated C include soluble microbial products as a sink for captured CO2. With the CO2 supply matched to the photosynthetic demand, light attenuation limited the rate microalgal photosynthesis. The DMCPBR presents an opportunity to improve CO2-deliver efficiency and make microalgae a more effective strategy for C-neutral resource recovery. PMID:26771923

  13. High-Level Accumulation of Triacylglycerol and Starch in Photoautotrophically Grown Chlamydomonas debaryana NIES-2212.

    PubMed

    Toyoshima, Masakazu; Sato, Naoki

    2015-12-01

    Microalgae have the potential to produce triacylglycerol (TAG) and starch, which provide alternative sources of biofuel. A problem in using Chlamydomonas reinhardtii as a model for TAG production has been that this alga lacks phosphatidylcholine (PC), which is thought to be important for TAG synthesis in plants. We found that C. debaryana is one of the rare species of Chlamydomonas having PC. Here we show that this strain, grown under complete photoautotrophic conditions, accumulated TAG and starch up to 20 and 250 pg per cell, respectively, during the stationary phase without nutrient deprivation. Addition of nutrients in this state did not cause loss of TAG, which was found in dilution with fresh medium. The photosynthetically produced TAG contained a high level of monounsaturated fatty acids, which is a preferred property as a material for biodiesel. The oil bodies were present in the cytoplasm, either between the cytoplasmic membrane and the chloroplast or between the chloroplast and the nucleus, whereas the starch granules were present within the chloroplast. Oil bodies were also deposited as a broad layer in the peripheral space of the cytoplasm outside the chloroplast, and might be easily released from the cells by genetic, chemical or mechanical manipulation. These results suggest that C. debaryana is a promising seed organism for developing a good biofuel producer. PMID:26542110

  14. Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease

    PubMed Central

    Aguilo, Francesca; Cecilia, Serena Di; Walsh, Martin J.

    2015-01-01

    The long non-coding RNA CDKN2B-AS1, commonly referred to as the Antisense Non-coding RNA in the INK4 Locus (ANRIL), is a 3.8-kb-long RNA transcribed from the short arm of human chromosome 9 on p21.3 that overlaps a critical region encompassing three major tumor suppressor loci juxtaposed to the INK4b-ARF-INK4a gene cluster and the methyl-thioadenosine phosphorylase (MTAP) gene. Genome-wide association studies have identified this region with a remarkable and growing number of disease-associated DNA alterations and single nucleotide polymorphisms, which corresponds to increased susceptibility to human disease. Recent attention has been devoted on whether these alterations in the ANRIL sequence affect its expression levels and/or its splicing transcript variation, and in consequence, global cellular homeostasis. Moreover, recent evidence postulates that ANRIL not only can regulate their immediate genomic neighbors in cis, but also has the capacity to regulate additional loci in trans. This action would further increase the complexity for mechanisms imposed through ANRIL and furthering the scope of this lncRNA in disease pathogenesis. In this chapter, we summarize the most recent findings on the investigation of ANRIL and provide a perspective on the biological and clinical significance of ANRIL as a putative biomarker, specifically, its potential role in directing cellular fates leading to cancer and cardiovascular disease. PMID:26220772

  15. Non-coding RNA: what is functional and what is junk?

    PubMed Central

    Palazzo, Alexander F.; Lee, Eliza S.

    2015-01-01

    The genomes of large multicellular eukaryotes are mostly comprised of non-protein coding DNA. Although there has been much agreement that a small fraction of these genomes has important biological functions, there has been much debate as to whether the rest contributes to development and/or homeostasis. Much of the speculation has centered on the genomic regions that are transcribed into RNA at some low level. Unfortunately these RNAs have been arbitrarily assigned various names, such as “intergenic RNA,” “long non-coding RNAs” etc., which have led to some confusion in the field. Many researchers believe that these transcripts represent a vast, unchartered world of functional non-coding RNAs (ncRNAs), simply because they exist. However, there are reasons to question this Panglossian view because it ignores our current understanding of how evolution shapes eukaryotic genomes and how the gene expression machinery works in eukaryotic cells. Although there are undoubtedly many more functional ncRNAs yet to be discovered and characterized, it is also likely that many of these transcripts are simply junk. Here, we discuss how to determine whether any given ncRNA has a function. Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk. PMID:25674102

  16. Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

    PubMed

    Shen, Yi; Katsaros, Dionyssios; Loo, Lenora W M; Hernandez, Brenda Y; Chong, Clayton; Canuto, Emilie Marion; Biglia, Nicoletta; Lu, Lingeng; Risch, Harvey; Chu, Wen-Ming; Yu, Herbert

    2015-04-20

    LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer. PMID:25865225

  17. Regulatory non-coding RNA: new instruments in the orchestration of cell death.

    PubMed

    Su, Ye; Wu, Haijiang; Pavlosky, Alexander; Zou, Ling-Lin; Deng, Xinna; Zhang, Zhu-Xu; Jevnikar, Anthony M

    2016-01-01

    Non-coding RNA (ncRNA) comprises a substantial portion of primary transcripts that are generated by genomic transcription, but are not translated into protein. The possible functions of these once considered 'junk' molecules have incited considerable interest and new insights have emerged. The two major members of ncRNAs, namely micro RNA (miRNA) and long non-coding RNA (lncRNA), have important regulatory roles in gene expression and many important physiological processes, which has recently been extended to programmed cell death. The previous paradigm of programmed cell death only by apoptosis has recently expanded to include modalities of regulated necrosis (RN), and particularly necroptosis. However, most research efforts in this field have been on protein regulators, leaving the role of ncRNAs largely unexplored. In this review, we discuss important findings concerning miRNAs and lncRNAs that modulate apoptosis and RN pathways, as well as the miRNA-lncRNA interactions that affect cell death regulation. PMID:27512954

  18. Targeting long non-coding RNAs in cancers: progress and prospects.

    PubMed

    Li, Chi Han; Chen, Yangchao

    2013-08-01

    Pervasive transcription occurs in the human genome to generate thousands of RNA transcripts, and accumulating evidence suggested that the RNA molecules, without protein coding ability, have important roles in diverse biological functions. Long non-coding RNA (lncRNA), with size larger than 200 nt, is a new class of the non-coding RNA that contributes to cancer development and progression. Roles for several lncRNAs in cancers have been characterized and strategies targeting them have inhibitory effects to malignant cells in vitro and in vivo. These findings point to the potential of lncRNAs as prospective novel therapeutic targets in cancers. Recent advance in biological drugs, led by nucleic acid drugs (i.e. siRNAs, antisense oligonucleotides), suggest directions for the development of cancer therapies targeting lncRNAs. Here, we discuss the characteristics of lncRNAs regarding their synthesis, stability and functional role in cells, and emphasize their unique properties that determine their molecular functions. We then discuss the association of lncRNAs with cancers, and illustrate the anticancer effects induced upon modulating the level and function of lncRNAs. We also revisit established methods for targeting RNA molecules and discuss new agents and strategies to attenuate lncRNAs in cancer. PMID:23748105

  19. Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer

    PubMed Central

    Shen, Yi; Katsaros, Dionyssios; Loo, Lenora W. M.; Hernandez, Brenda Y.; Chong, Clayton; Canuto, Emilie Marion; Biglia, Nicoletta; Lu, Lingeng; Risch, Harvey; Chu, Wen-Ming; Yu, Herbert

    2015-01-01

    LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer. PMID:25865225

  20. Long non-coding RNA MINCR promotes gallbladder cancer progression through stimulating EZH2 expression.

    PubMed

    Wang, Shou-Hua; Yang, Yong; Wu, Xiao-Cai; Zhang, Ming-Di; Weng, Ming-Zhe; Zhou, Di; Wang, Jian-Dong; Quan, Zhi-Wei

    2016-09-28

    The regulation of MYC-regulated long non-coding RNAs has been reported to contribute to certain types of cancers. However, the role of MYC-induced long non-coding RNA (MINCR) in the tumorigenesis of gallbladder cancer (GBC) is still largely unknown. In this study, we discovered that MINCR was markedly upregulated in GBC tissues compared with adjacent normal tissues. High MINCR expression levels in GBC were positively associated with tumor volume and lymph node metastasis and were negatively correlated with overall survival (OS). Upregulation of MINCR and enhancer of zeste homolog 2 (EZH2) in GBC coincided with the downregulation of miR-26a-5p in GBC. Mechanistically, MINCR/miR-26a-5p/EZH2 axis was found to be involved in cell proliferation, cell invasive and apoptosis in GBC cells. Moreover, knockdown of MINCR suppressed cell proliferation, decreased S-phase cell numbers, increased cell apoptosis, and inhibited cell invasion by inhibiting the epithelial-mesenchymal transition (EMT) phenomenon in GBC cells. In vivo, tumor volumes were significantly decreased in the MINCR silencing group compared with those in the control group. These results demonstrated that MINCR could potentially be a therapeutic target as well as a prognostic marker in GBC. PMID:27345740

  1. Role of long non-coding RNAs in the determination of β-cell identity.

    PubMed

    Motterle, A; Sanchez-Parra, C; Regazzi, R

    2016-09-01

    Pancreatic β-cells are highly specialized cells committed to secrete insulin in response to changes in the level of nutrients, hormones and neurotransmitters. Chronic exposure to elevated concentrations of glucose, fatty acids or inflammatory mediators can result in modifications in β-cell gene expression that alter their functional properties. This can lead to the release of insufficient amount of insulin to cover the organism's needs, and thus to the development of diabetes mellitus. Although most of the studies carried out in the last decades to elucidate the causes of β-cell dysfunction under disease conditions have focused on protein-coding genes, we now know that insulin-secreting cells also contain thousands of molecules of RNA that do not encode polypeptides but play key roles in the acquisition and maintenance of a highly differentiated state. In this review, we will highlight the involvement of long non-coding RNAs (lncRNAs), a particular class of non-coding transcripts, in the differentiation of β-cells and in the regulation of their specialized tasks. We will also discuss the crosstalk between the activities of lncRNAs and microRNAs and present the emerging evidence of a potential contribution of particular lncRNAs to the development of both type 1 and type 2 diabetes. PMID:27615130

  2. Estradiol-Induced Transcriptional Regulation of Long Non-Coding RNA, HOTAIR.

    PubMed

    Bhan, Arunoday; Mandal, Subhrangsu S

    2016-01-01

    HOTAIR (HOX antisense intergenic RNA) is a 2.2 kb long non-coding RNA (lncRNA), transcribed from the antisense strand of homeobox C (HOXC) gene locus in chromosome 12. HOTAIR acts as a scaffolding lncRNA. It interacts and guides various chromatin-modifying complexes such as PRC2 (polycomb-repressive complex 2) and LSD1 (lysine-specific demethylase 1) to the target gene promoters leading to their gene silencing. Various studies have demonstrated that HOTAIR overexpression is associated with breast cancer. Recent studies from our laboratory demonstrate that HOTAIR is required for viability of breast cancer cells and is transcriptionally regulated by estradiol (E2) in vitro and in vivo. This chapter describes protocols for analysis of the HOTAIR promoter, cloning, transfection and dual luciferase assays, knockdown of protein synthesis by antisense oligonucleotides, and chromatin immunoprecipitation (ChIP) assay. These protocols are useful for studying the estrogen-mediated transcriptional regulation of lncRNA HOTAIR, as well as other protein coding genes and non-coding RNAs. PMID:26585152

  3. Junk DNA and the long non-coding RNA twist in cancer genetics

    PubMed Central

    Ling, Hui; Vincent, Kimberly; Pichler, Martin; Fodde, Riccardo; Berindan-Neagoe, Ioana; Slack, Frank J.; Calin, George A

    2015-01-01

    The central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs (lncRNAs) have attracted much attention due to their large number and biological significance. Many lncRNAs have been identified as mapping to regulatory elements including gene promoters and enhancers, ultraconserved regions, and intergenic regions of protein-coding genes. Yet, the biological function and molecular mechanisms of lncRNA in human diseases in general and cancer in particular remain largely unknown. Data from the literature suggest that lncRNA, often via interaction with proteins, functions in specific genomic loci or use their own transcription loci for regulatory activity. In this review, we summarize recent findings supporting the importance of DNA loci in lncRNA function, and the underlying molecular mechanisms via cis or trans regulation, and discuss their implications in cancer. In addition, we use the 8q24 genomic locus, a region containing interactive SNPs, DNA regulatory elements and lncRNAs, as an example to illustrate how single nucleotide polymorphism (SNP) located within lncRNAs may be functionally associated with the individual’s susceptibility to cancer. PMID:25619839

  4. Functional non-coding RNAs derived from the flavivirus 3' untranslated region.

    PubMed

    Clarke, B D; Roby, J A; Slonchak, A; Khromykh, A A

    2015-08-01

    Flaviviruses are single-stranded positive sense RNA enveloped viruses. The flavivirus genus includes important human pathogens such as dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Murray Valley encephalitis virus (MVEV). In addition to the viral proteins and viral genomic RNA, flaviviruses produce at least two functional non-coding RNAs derived from the 3' untranslated region (3'UTR), the subgenomic flavivirus RNA (sfRNA) and a putative WNV miRNA (KUN-miR-1). In this review we summarize published data from studies with WNV, YFV, DENV, JEV, and MVEV on sfRNA production following incomplete degradation of the viral genomic RNA by the cellular 5'-3' exoribonuclease 1 (XRN1), RNA structural elements involved in stalling XRN1 to generate sfRNA, and functions of sfRNA in modulating cellular mRNA decay and RNAi pathways as well as in modulating anti-viral type I interferon response. In addition, we also summarize data on the mechanisms of biogenesis of 3'UTR-derived KUN-miR-1 and its function in WNV replication in mosquito host, along with recent findings on a discovery of a second potential flaviviral miRNA vsRNA5, derived from the 3'UTR of DENV. This review thus summarizes the known mechanisms of generation and the functions of flaviviral 3'UTR-derived non-coding RNAs. PMID:25660582

  5. An integrative approach to predicting the functional effects of non-coding and coding sequence variation

    PubMed Central

    Shihab, Hashem A.; Rogers, Mark F.; Gough, Julian; Mort, Matthew; Cooper, David N.; Day, Ian N. M.; Gaunt, Tom R.; Campbell, Colin

    2015-01-01

    Motivation: Technological advances have enabled the identification of an increasingly large spectrum of single nucleotide variants within the human genome, many of which may be associated with monogenic disease or complex traits. Here, we propose an integrative approach, named FATHMM-MKL, to predict the functional consequences of both coding and non-coding sequence variants. Our method utilizes various genomic annotations, which have recently become available, and learns to weight the significance of each component annotation source. Results: We show that our method outperforms current state-of-the-art algorithms, CADD and GWAVA, when predicting the functional consequences of non-coding variants. In addition, FATHMM-MKL is comparable to the best of these algorithms when predicting the impact of coding variants. The method includes a confidence measure to rank order predictions. Availability and implementation: The FATHMM-MKL webserver is available at: http://fathmm.biocompute.org.uk Contact: H.Shihab@bristol.ac.uk or Mark.Rogers@bristol.ac.uk or C.Campbell@bristol.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25583119

  6. Non-coding RNA and Antisense RNA. Nature's Trash or Treasure?

    PubMed Central

    Knowling, Stuart; Morris, Kevin V.

    2011-01-01

    Although control of cellular function has classically been considered the responsibility of proteins, research over the last decade has elucidated many roles for RNA in regulation of not only the proteins that control cellular functions but also for the cellular functions themselves. In parallel to this advancement in knowledge about the regulatory roles of RNA there has been an explosion of knowledge about the role that epigenetics plays in controlling not only long-term cellular fate but also the short-term regulatory control of genes. Of particular interest is the crossover between these two worlds, a world where RNA can act out its part and subsequently elicit chromatin modifications that alter cellular function. Two main categories of RNA are examined here, non-coding RNA and antisense RNA both of which perform vital functions in controlling numerous genes, proteins and RNA itself. As the activities of non-coding and antisense RNA in both normal and aberrant cellular function are elucidated, so does the number of possible targets for pharmacopeic intervention. PMID:21843589

  7. The Role of Long Non-Coding RNAs in Breast Cancer.

    PubMed

    Soudyab, Mohammad; Iranpour, Mostafa; Ghafouri-Fard, Soudeh

    2016-07-01

    Long non-coding RNA (lncRNA) genes are an important population of non-coding RNAs with defined key roles in normal development as well as tumorigenesis process. Evidences suggest that they can be classified as tumor suppressor genes or oncogenes according to their functions and expression pattern in tumoral tissues. They have been shown to regulate the plasticity of cancer stem cells. Their important roles in the regulation of cancer-related pathways in addition to deregulation of their expression in a number of cancers have suggested that they can be used as markers for cancer detection and prognosis, as well as targets for cancer treatment. Deregulation of a number of lncRNAs, such as HOTAIR, XIST, MALAT, and H19 has been detected in breast cancer samples and cell lines. In addition, the association between lncRNAs signature and breast cancer patients' survival has been assessed in various studies. Here, the expression patterns of lncRNAs in breast cancer, as well as their significance in prognosis and patient treatment are discussed. PMID:27362246

  8. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    SciTech Connect

    Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen; Catalano, Jennifer; Yamada, Kenneth M.; Dhawan, Subhash

    2014-11-07

    Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.

  9. Comprehensive Reconstruction and Visualization of Non-Coding Regulatory Networks in Human

    PubMed Central

    Bonnici, Vincenzo; Russo, Francesco; Bombieri, Nicola; Pulvirenti, Alfredo; Giugno, Rosalba

    2014-01-01

    Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape. PMID:25540777

  10. Comprehensive reconstruction and visualization of non-coding regulatory networks in human.

    PubMed

    Bonnici, Vincenzo; Russo, Francesco; Bombieri, Nicola; Pulvirenti, Alfredo; Giugno, Rosalba

    2014-01-01

    Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape. PMID:25540777

  11. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans

    PubMed Central

    Holdt, Lesca M.; Stahringer, Anika; Sass, Kristina; Pichler, Garwin; Kulak, Nils A.; Wilfert, Wolfgang; Kohlmaier, Alexander; Herbst, Andreas; Northoff, Bernd H.; Nicolaou, Alexandros; Gäbel, Gabor; Beutner, Frank; Scholz, Markus; Thiery, Joachim; Musunuru, Kiran; Krohn, Knut; Mann, Matthias; Teupser, Daniel

    2016-01-01

    Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their molecular mechanism in human disease remains obscure. Here we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers atheroprotection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. CircANRIL binds to pescadillo homologue 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key cell functions in atherosclerosis. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring atheroprotection, thereby showing that circularization of long non-coding RNAs may alter RNA function and protect from human disease. PMID:27539542

  12. Long Non-Coding RNAs As Potential Novel Prognostic Biomarkers in Colorectal Cancer

    PubMed Central

    Saus, Ester; Brunet-Vega, Anna; Iraola-Guzmán, Susana; Pegueroles, Cinta; Gabaldón, Toni; Pericay, Carles

    2016-01-01

    Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Surgery is usually the first line of treatment for patients with CRC but many tumors with similar histopathological features show significantly different clinical outcomes. The discovery of robust prognostic biomarkers in patients with CRC is imperative to achieve more effective treatment strategies and improve patient's care. Recent progress in next generation sequencing methods and transcriptome analysis has revealed that a much larger part of the genome is transcribed into RNA than previously assumed. Collectively referred to as non-coding RNAs (ncRNAs), some of these RNA molecules such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been shown to be altered and to play critical roles in tumor biology. This discovery leads to exciting possibilities for personalized cancer diagnosis, and therapy. Many lncRNAs are tissue and cancer-type specific and have already revealed to be useful as prognostic markers. In this review, we focus on recent findings concerning aberrant expression of lncRNAs in CRC tumors and emphasize their prognostic potential in CRC. Further studies focused on the mechanisms of action of lncRNAs will contribute to the development of novel biomarkers for diagnosis and disease progression. PMID:27148353

  13. The interplay of long non-coding RNAs and MYC in cancer

    PubMed Central

    Hamilton, Michael J.; Young, Matthew D.; Sauer, Silvia; Martinez, Ernest

    2016-01-01

    Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are changing how researchers view eukaryotic gene regulation. Once considered to be non-functional products of low-level aberrant transcription from non-coding regions of the genome, lncRNAs are now viewed as important epigenetic regulators and several lncRNAs have now been demonstrated to be critical players in the development and/or maintenance of cancer. Similarly, the emerging variety of interactions between lncRNAs and MYC, a well-known oncogenic transcription factor linked to most types of cancer, have caught the attention of many biomedical researchers. Investigations exploring the dynamic interactions between lncRNAs and MYC, referred to as the lncRNA-MYC network, have proven to be especially complex. Genome-wide studies have shown that MYC transcriptionally regulates many lncRNA genes. Conversely, recent reports identified lncRNAs that regulate MYC expression both at the transcriptional and post-transcriptional levels. These findings are of particular interest because they suggest roles of lncRNAs as regulators of MYC oncogenic functions and the possibility that targeting lncRNAs could represent a novel avenue to cancer treatment. Here, we briefly review the current understanding of how lncRNAs regulate chromatin structure and gene transcription, and then focus on the new developments in the emerging field exploring the lncRNA-MYC network in cancer. PMID:27077133

  14. Evaluation of temporary non-code repairs in safety class 3 piping systems

    SciTech Connect

    Godha, P.C.; Kupinski, M.; Azevedo, N.F.

    1996-12-01

    Temporary non-ASME Code repairs in safety class 3 pipe and piping components are permissible during plant operation in accordance with Nuclear Regulatory Commission Generic Letter 90-05. However, regulatory acceptance of such repairs requires the licensee to undertake several timely actions. Consistent with the requirements of GL 90-05, this paper presents an overview of the detailed evaluation and relief request process. The technical criteria encompasses both ductile and brittle piping materials. It also lists appropriate evaluation methods that a utility engineer can select to perform a structural integrity assessment for design basis loading conditions to support the use of temporary non-Code repair for degraded piping components. Most use of temporary non-code repairs at a nuclear generating station is in the service water system which is an essential safety related system providing the ultimate heat sink for various plant systems. Depending on the plant siting, the service water system may use fresh water or salt water as the cooling medium. Various degradation mechanisms including general corrosion, erosion/corrosion, pitting, microbiological corrosion, galvanic corrosion, under-deposit corrosion or a combination thereof continually challenge the pressure boundary structural integrity. A good source for description of corrosion degradation in cooling water systems is provided in a cited reference.

  15. The Emerging Role of Non-Coding RNAs in Drug Addiction

    PubMed Central

    Sartor, Gregory C.; St. Laurent, Georges; Wahlestedt, Claes

    2012-01-01

    Prolonged drug use causes long-lasting neuroadaptations in reward-related brain areas that contribute to addiction. Despite significant amount of research dedicated to understanding the underlying mechanisms of addiction, the molecular underpinnings remain unclear. At the same time, much of the pervasive transcription that encompasses the human genome occurs in the nervous system and contributes to its heterogeneity and complexity. Recent evidence suggests that non-coding RNAs (ncRNAs) play an important and dynamic role in transcriptional regulation, epigenetic signaling, stress response, and plasticity in the nervous system. Dysregulation of ncRNAs are thought to contribute to many, and perhaps all, neurological disorders, including addiction. Here, we review recent insights in the functional relevance of ncRNAs, including both microRNAs (miRNAs), and long non-coding RNAs, and then illustrate specific examples of ncRNA regulation in the context of drug addiction. We conclude that ncRNAs are importantly involved in the persistent neuroadaptations associated with addiction-related behaviors, and that therapies that target specific ncRNAs may represent new avenues for the treatment of drug addiction. PMID:22737160

  16. Role of non-coding RNAs in pancreatic cancer: The bane of the microworld

    PubMed Central

    Tang, Yi-Ting; Xu, Xiao-Hui; Yang, Xiao-Dong; Hao, Jun; Cao, Han; Zhu, Wei; Zhang, Shu-Yu; Cao, Jian-Ping

    2014-01-01

    Our understanding of the mechanisms underlying the development of pancreatic cancer has been greatly advanced. However, the molecular events involved in the initiation and development of pancreatic cancer remain inscrutable. None of the present medical technologies have been proven to be effective in significantly improving early detection or reducing the mortality/morbidity of this disease. Thus, a better understanding of the molecular basis of pancreatic cancer is required for the identification of more effective diagnostic markers and therapeutic targets. Non-coding RNAs (ncRNAs), generally including microRNAs and long non-coding RNAs, have recently been found to be deregulated in many human cancers, which provides new opportunities for identifying both functional drivers and specific biomarkers of pancreatic cancer. In this article, we review the existing literature in the field documenting the significance of aberrantly expressed and functional ncRNAs in human pancreatic cancer, and discuss how oncogenic ncRNAs may be involved in the genetic and epigenetic networks regulating functional pathways that are deregulated in this malignancy, particularly of the ncRNAs’ role in drug resistance and epithelial-mesenchymal transition biological phenotype, with the aim of analyzing the feasibility of clinical application of ncRNAs in the diagnosis and treatment of pancreatic cancer. PMID:25071335

  17. Long Non-coding RNA in Neurons: New Players in Early Response to BDNF Stimulation

    PubMed Central

    Aliperti, Vincenza; Donizetti, Aldo

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin family member that is highly expressed and widely distributed in the brain. BDNF is critical for neural survival and plasticity both during development and in adulthood, and dysfunction in its signaling may contribute to a number of neurodegenerative disorders. Deep understanding of the BDNF-activated molecular cascade may thus help to find new biomarkers and therapeutic targets. One interesting direction is related to the early phase of BDNF-dependent gene expression regulation, which is responsible for the activation of selective gene programs that lead to stable functional and structural remodeling of neurons. Immediate-early coding genes activated by BDNF are under investigation, but the involvement of the non-coding RNAs is largely unexplored, especially the long non-coding RNAs (lncRNAs). lncRNAs are emerging as key regulators that can orchestrate different aspects of nervous system development, homeostasis, and plasticity, making them attractive candidate markers and therapeutic targets for brain diseases. We used microarray technology to identify differentially expressed lncRNAs in the immediate response phase of BDNF stimulation in a neuronal cell model. Our observations on the putative functional role of lncRNAs provide clues to their involvement as master regulators of gene expression cascade triggered by BDNF. PMID:26973456

  18. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans.

    PubMed

    Holdt, Lesca M; Stahringer, Anika; Sass, Kristina; Pichler, Garwin; Kulak, Nils A; Wilfert, Wolfgang; Kohlmaier, Alexander; Herbst, Andreas; Northoff, Bernd H; Nicolaou, Alexandros; Gäbel, Gabor; Beutner, Frank; Scholz, Markus; Thiery, Joachim; Musunuru, Kiran; Krohn, Knut; Mann, Matthias; Teupser, Daniel

    2016-01-01

    Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their molecular mechanism in human disease remains obscure. Here we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers atheroprotection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. CircANRIL binds to pescadillo homologue 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key cell functions in atherosclerosis. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring atheroprotection, thereby showing that circularization of long non-coding RNAs may alter RNA function and protect from human disease. PMID:27539542

  19. Junk DNA and the long non-coding RNA twist in cancer genetics.

    PubMed

    Ling, H; Vincent, K; Pichler, M; Fodde, R; Berindan-Neagoe, I; Slack, F J; Calin, G A

    2015-09-24

    The central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs (lncRNAs) have attracted much attention due to their large number and biological significance. Many lncRNAs have been identified as mapping to regulatory elements including gene promoters and enhancers, ultraconserved regions and intergenic regions of protein-coding genes. Yet, the biological function and molecular mechanisms of lncRNA in human diseases in general and cancer in particular remain largely unknown. Data from the literature suggest that lncRNA, often via interaction with proteins, functions in specific genomic loci or use their own transcription loci for regulatory activity. In this review, we summarize recent findings supporting the importance of DNA loci in lncRNA function and the underlying molecular mechanisms via cis or trans regulation, and discuss their implications in cancer. In addition, we use the 8q24 genomic locus, a region containing interactive SNPs, DNA regulatory elements and lncRNAs, as an example to illustrate how single-nucleotide polymorphism (SNP) located within lncRNAs may be functionally associated with the individual's susceptibility to cancer. PMID:25619839

  20. Structural architecture of the human long non-coding RNA, steroid receptor RNA activator.

    PubMed

    Novikova, Irina V; Hennelly, Scott P; Sanbonmatsu, Karissa Y

    2012-06-01

    While functional roles of several long non-coding RNAs (lncRNAs) have been determined, the molecular mechanisms are not well understood. Here, we report the first experimentally derived secondary structure of a human lncRNA, the steroid receptor RNA activator (SRA), 0.87 kB in size. The SRA RNA is a non-coding RNA that coactivates several human sex hormone receptors and is strongly associated with breast cancer. Coding isoforms of SRA are also expressed to produce proteins, making the SRA gene a unique bifunctional system. Our experimental findings (SHAPE, in-line, DMS and RNase V1 probing) reveal that this lncRNA has a complex structural organization, consisting of four domains, with a variety of secondary structure elements. We examine the coevolution of the SRA gene at the RNA structure and protein structure levels using comparative sequence analysis across vertebrates. Rapid evolutionary stabilization of RNA structure, combined with frame-disrupting mutations in conserved regions, suggests that evolutionary pressure preserves the RNA structural core rather than its translational product. We perform similar experiments on alternatively spliced SRA isoforms to assess their structural features. PMID:22362738

  1. Structural architecture of the human long non-coding RNA, steroid receptor RNA activator

    PubMed Central

    Novikova, Irina V.; Hennelly, Scott P.; Sanbonmatsu, Karissa Y.

    2012-01-01

    While functional roles of several long non-coding RNAs (lncRNAs) have been determined, the molecular mechanisms are not well understood. Here, we report the first experimentally derived secondary structure of a human lncRNA, the steroid receptor RNA activator (SRA), 0.87 kB in size. The SRA RNA is a non-coding RNA that coactivates several human sex hormone receptors and is strongly associated with breast cancer. Coding isoforms of SRA are also expressed to produce proteins, making the SRA gene a unique bifunctional system. Our experimental findings (SHAPE, in-line, DMS and RNase V1 probing) reveal that this lncRNA has a complex structural organization, consisting of four domains, with a variety of secondary structure elements. We examine the coevolution of the SRA gene at the RNA structure and protein structure levels using comparative sequence analysis across vertebrates. Rapid evolutionary stabilization of RNA structure, combined with frame-disrupting mutations in conserved regions, suggests that evolutionary pressure preserves the RNA structural core rather than its translational product. We perform similar experiments on alternatively spliced SRA isoforms to assess their structural features. PMID:22362738

  2. Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges.

    PubMed

    Yu, T; Li, C; Wang, Z; Liu, K; Xu, C; Yang, Q; Tang, Y; Wu, Y

    2016-05-01

    Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication. PMID:26370423

  3. NONCODE 2016: an informative and valuable data source of long non-coding RNAs

    PubMed Central

    Zhao, Yi; Li, Hui; Fang, Shuangsang; Kang, Yue; wu, Wei; Hao, Yajing; Li, Ziyang; Bu, Dechao; Sun, Ninghui; Zhang, Michael Q.; Chen, Runsheng

    2016-01-01

    NONCODE (http://www.bioinfo.org/noncode/) is an interactive database that aims to present the most complete collection and annotation of non-coding RNAs, especially long non-coding RNAs (lncRNAs). The recently reduced cost of RNA sequencing has produced an explosion of newly identified data. Revolutionary third-generation sequencing methods have also contributed to more accurate annotations. Accumulative experimental data also provides more comprehensive knowledge of lncRNA functions. In this update, NONCODE has added six new species, bringing the total to 16 species altogether. The lncRNAs in NONCODE have increased from 210 831 to 527,336. For human and mouse, the lncRNA numbers are 167,150 and 130,558, respectively. NONCODE 2016 has also introduced three important new features: (i) conservation annotation; (ii) the relationships between lncRNAs and diseases; and (iii) an interface to choose high-quality datasets through predicted scores, literature support and long-read sequencing method support. NONCODE is also accessible through http://www.noncode.org/. PMID:26586799

  4. Bioactivity of Benthic and Picoplanktonic Estuarine Cyanobacteria on Growth of Photoautotrophs: Inhibition versus Stimulation

    PubMed Central

    Lopes, Viviana R.; Vasconcelos, Vitor M.

    2011-01-01

    Understanding potential biochemical interactions and effects among cyanobacteria and other organisms is one of the main keys to a better knowledge of microbial population structuring and dynamics. In this study, the effects of cyanobacteria from benthos and plankton of estuaries on other cyanobacteria and green algae growth were evaluated. To understand how the estuarine cyanobacteria might influence the dynamics of phytoplankton, experiments were carried out with the freshwater species Microcystis aeruginosa and Chlorella sp., and the marine Synechocystis salina and Nannochloropsis sp. exposed to aqueous and organic (70% methanol) crude extracts of cyanobacteria for 96 h. The most pronounced effect observed was the growth stimulation. Growth inhibition was also observed for S. salina and M. aeruginosa target-species at the highest and lowest concentrations of cyanobacterial extracts. The methanolic crude extract of Phormidium cf. chalybeum LEGE06078 was effective against S. salina growth in a concentration-dependent manner after 96 h-exposure. All of the cyanobacterial isolates showed some bioactivity on the target-species growth, i.e., inhibitory or stimulating effects. These results indicate that the analyzed cyanobacterial isolates can potentially contribute to blooms’ proliferation of other cyanobacteria and to the abnormal growth of green algae disturbing the dynamic of estuarine phytoplankton communities. Since estuaries are transitional ecosystems, the benthic and picoplanktonic estuarine cyanobacteria can change both freshwater and marine phytoplankton succession, competition and bloom formation. Furthermore, a potential biotechnological application of these isolates as a tool to control cyanobacteria and microalgae proliferation can be feasible. This work is the first on the subject of growth responses of photoautotrophs to cyanobacteria from Atlantic estuarine environments. PMID:21673889

  5. Multifunctional non-coding Epstein-Barr virus encoded RNAs (EBERs) contribute to viral pathogenesis.

    PubMed

    Iwakiri, Dai

    2016-01-01

    Epstein-Barr Virus (EBV) is known as an oncogenic herpesvirus implicated in the pathogenesis of various malignancies. It has been reported that EBV non-coding RNAs (ncRNAs) including EBV-encoded small RNAs (EBERs) and EBV-miRNAs contribute to viral pathogenesis. EBERs that are expressed abundantly in latently EBV-infected cells have been reported to play significant roles in tumorigenesis by EBV. Furthermore, it was demonstrated that the modulation of host innate immune signals by EBERs contributes to EBV-mediated pathogenesis including oncogenesis. Recently it was demonstrated that EBERs are secreted via exosomes by EBV-infected cells. It was also demonstrated that exosomes contain a number of EBV-encoded miRNAs. Various mRNAs have been identified as targets for regulation by EBV-miRNAs in host cells, therefore, EBERs and EBV-miRNAs might function through the transfer of exosomes. PMID:26292159

  6. A-to-I editing of coding and non-coding RNAs by ADARs

    PubMed Central

    Nishikura, Kazuko

    2016-01-01

    Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. This A-to-I editing occurs not only in protein-coding regions of mRNAs, but also frequently in non-coding regions that contain inverted Alu repeats. Editing of coding sequences can result in the expression of functionally altered proteins that are not encoded in the genome, whereas the significance of Alu editing remains largely unknown. Certain microRNA (miRNA) precursors are also edited, leading to reduced expression or altered function of mature miRNAs. Conversely, recent studies indicate that ADAR1 forms a complex with Dicer to promote miRNA processing, revealing a new function of ADAR1 in the regulation of RNA interference. PMID:26648264

  7. Long non-coding RNAs as novel therapeutic targets in cancer.

    PubMed

    Lavorgna, Giovanni; Vago, Riccardo; Sarmini, Mohamad; Montorsi, Francesco; Salonia, Andrea; Bellone, Matteo

    2016-08-01

    Thanks to impressive technology advancements, pervasive expression of non-coding RNAs (ncRNAs) has been recently identified in the genome of numerous cancers. Long ncRNAs (lncRNAs) belong to a new class of ncRNAs including tens of thousands different species. A fraction of these molecules shows a striking cancer-enriched expression pattern, suggesting an essential role in tumor cells and, possibly, a utility in therapeutic terms. This review aims at summarizing current knowledge for the identification and validation of lncRNAs as therapeutics targets in tumors. Both in-silico and wet-biology resources are presented in relation to the many challenges that the scientific community still needs to address in terms of lncRNA identification, stratification, patient personalization, drug delivery and toxicity. PMID:27210721

  8. Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma.

    PubMed

    Seles, Maximilian; Hutterer, Georg C; Kiesslich, Tobias; Pummer, Karl; Berindan-Neagoe, Ioana; Perakis, Samantha; Schwarzenbacher, Daniela; Stotz, Michael; Gerger, Armin; Pichler, Martin

    2016-01-01

    Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future. PMID:27092491

  9. The functional role of long non-coding RNAs and epigenetics

    PubMed Central

    2014-01-01

    Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. The post-transcriptional regulation is influenced by these lncRNAs by interfering with the microRNA pathways, involving in diverse cellular processes. The regulation of gene expression by lncRNAs at the epigenetic level, transcriptional and post-transcriptional level have been well known and widely studied. Recent recognition that lncRNAs make effects in many biological and pathological processes such as stem cell pluripotency, neurogenesis, oncogenesis and etc. This review will focus on the functional roles of lncRNAs in epigenetics and related research progress will be summarized. PMID:25276098

  10. Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma

    PubMed Central

    Seles, Maximilian; Hutterer, Georg C.; Kiesslich, Tobias; Pummer, Karl; Berindan-Neagoe, Ioana; Perakis, Samantha; Schwarzenbacher, Daniela; Stotz, Michael; Gerger, Armin; Pichler, Martin

    2016-01-01

    Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future. PMID:27092491

  11. Regulation of neuronal-glial fate specification by long non-coding RNAs.

    PubMed

    Wang, Lei; Liu, Yan; Sun, Shaiqi; Lu, Ming; Xia, Ying

    2016-07-01

    Neural stem cell transplantation is becoming a promising and attractive cell-based treatment modality for repairing the damaged central nervous system. One of the limitations of this approach is that the proportion of functional cells differentiated from stem cells still remains at a low level. In recent years, novel long non-coding RNAs (lncRNAs) are being discovered at a growing pace, suggesting that this class of molecules may act as novel regulators in neuronal-glial fate specification. In this review, we first describe the general features of lncRNAs that are more likely to be relevant to reveal their function. By this, we aim to point out the specific roles of a number of lncRNAs whose function has been described during neuronal and glial cell differentiation. There is no doubt that investigation of the lncRNAs will open a new window in studying neuronal-glial fate specification. PMID:26943605

  12. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs). Corrected Copy, Aug. 25, 2014

    NASA Technical Reports Server (NTRS)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This report contains the outcome of the assessment and the findings, observations, and NESC recommendations to the Agency and individual NASA Centers.

  13. Long non-coding RNAs and cancer: a new frontier of translational research?

    PubMed Central

    Spizzo, R; Almeida, MI; Colombatti, A; Calin, GA

    2012-01-01

    Tiling array and novel sequencing technologies have made available the transcription profile of the entire human genome. However, the extent of transcription and the function of genetic elements that occur outside of protein-coding genes, particularly those involved in disease, are still a matter of debate. In this review, we focus on long non-coding RNAs (lncRNAs) that are involved in cancer. We define lncRNAs and present a cancer-oriented list of lncRNAs, list some tools (for example, public databases) that classify lncRNAs or that scan genome spans of interest to find whether known lncRNAs reside there, and describe some of the functions of lncRNAs and the possible genetic mechanisms that underlie lncRNA expression changes in cancer, as well as current and potential future applications of lncRNA research in the treatment of cancer. PMID:22266873

  14. The role of non-coding RNAs in male sex determination and differentiation.

    PubMed

    Rastetter, Raphael H; Smith, Craig A; Wilhelm, Dagmar

    2015-09-01

    A complex network of gene regulation and interaction drives male sex determination and differentiation. While many important protein-coding genes that are necessary for proper male development have been identified, many disorders in human sex development are still unexplained at the molecular level. This suggests that key factors and regulatory mechanisms are still unknown. In recent years, extensive data have shown that different classes of non-coding RNAs (ncRNAs) play a role in almost all developmental and physiological pathways. Here we review what is known about their role in male sex determination and differentiation not only in mammals, but also other species. While for some processes a key role for ncRNA has been identified, we are still far from having a complete picture. PMID:25995439

  15. Non-coding RNAs: novel players in chromatin-regulation during viral latency.

    PubMed

    Eilebrecht, Sebastian; Schwartz, Christian; Rohr, Olivier

    2013-08-01

    Chromatin structure plays an essential role during gene expression regulation not only in the case of the host cellular genome, but also during the viral life cycle. Epigenetic chromatin marks thereby define, whether a gene promoter is accessible for the transcription machinery or whether a repressive heterochromatin state is established. The heterochromatin-mediated repression of lytic viral genes results in viral latency, enabling the virus to persist dormant without being recognized by the host immune system, but keeping the potential for reactivation. Arising new systems biology approaches are starting to uncover an unexpected multiplicity and variety of non-coding (nc)RNAs playing important roles during chromatin structure control, likely constituting a novel layer in epigenetic regulation. In this review we give an overview of chromatin-regulatory viral and host cellular ncRNAs and their links to viral latency. PMID:23660570

  16. Long non-coding RNAs in heart failure: an obvious lnc

    PubMed Central

    El Azzouzi, Hamid; Doevendans, Pieter Adrianus

    2016-01-01

    Heart failure is a life-threatening and costly ailment characterized by structural and functional impairment of the heart. Despite major advances in understanding protein-mediated transcriptional control and signaling pathways that underlie the cellular and interstitial alterations of heart failure, significant therapeutical breakthroughs for innovative treatments of this disease are still missing. The recent extensive profiling of the mammalian transcriptome has revealed a large number of long non-coding RNAs (lncRNAs) that play a diversity of important regulatory roles in gene expression. In here, we focus on a recent work by Ounzain and colleagues comprising genome-wide profiling of the cardiac transcriptome after myocardial infarction with an emphasis on the identification of novel heart-specific lncRNAs. PMID:27275495

  17. Rise of the RNA machines: exploring the structure of long non-coding RNAs.

    PubMed

    Novikova, Irina V; Hennelly, Scott P; Tung, Chang-Shung; Sanbonmatsu, Karissa Y

    2013-10-01

    Novel, profound and unexpected roles of long non-coding RNAs (lncRNAs) are emerging in critical aspects of gene regulation. Thousands of lncRNAs have been recently discovered in a wide range of mammalian systems, related to development, epigenetics, cancer, brain function and hereditary disease. The structural biology of these lncRNAs presents a brave new RNA world, which may contain a diverse zoo of new architectures and mechanisms. While structural studies of lncRNAs are in their infancy, we describe existing structural data for lncRNAs, as well as crystallographic studies of other RNA machines and their implications for lncRNAs. We also discuss the importance of dynamics in RNA machine mechanism. Determining commonalities between lncRNA systems will help elucidate the evolution and mechanistic role of lncRNAs in disease, creating a structural framework necessary to pursue lncRNA-based therapeutics. PMID:23467124

  18. Non-coding RNAs as direct and indirect modulators of epigenetic regulation

    PubMed Central

    Peschansky, Veronica J; Wahlestedt, Claes

    2014-01-01

    Epigenetic regulation of gene expression is an increasingly well-understood concept that explains much of the contribution of an organism’s environment and experience to its biology. However, discussion persists as to which mechanisms can be classified as epigenetic. Ongoing research continues to uncover novel pathways, including the important role of non-protein coding RNA transcripts in epigenetic gene regulation. We know that the majority of human and other mammalian transcripts are not translated but that many of these are nonetheless functional. These non-coding RNAs (ncRNAs) can be short (< 200 nt) or long (< 200 nt) and are further classified by genomic origin and mechanism of action. We discuss examples of ncRNAs that interact with histone modifying complexes or DNA methyltransferases to regulate gene expression, others that are targets of these epigenetic mechanisms, and propose a model in which such transcripts feed back into an epigenetic regulatory network. PMID:24739571

  19. Role of Non-Coding RNAs in the Transgenerational Epigenetic Transmission of the Effects of Reprotoxicants

    PubMed Central

    Larriba, Eduardo; del Mazo, Jesús

    2016-01-01

    Non-coding RNAs (ncRNAs) are regulatory elements of gene expression and chromatin structure. Both long and small ncRNAs can also act as inductors and targets of epigenetic programs. Epigenetic patterns can be transmitted from one cell to the daughter cell, but, importantly, also through generations. Diversity of ncRNAs is emerging with new and surprising roles. Functional interactions among ncRNAs and between specific ncRNAs and structural elements of the chromatin are drawing a complex landscape. In this scenario, epigenetic changes induced by environmental stressors, including reprotoxicants, can explain some transgenerationally-transmitted phenotypes in non-Mendelian ways. In this review, we analyze mechanisms of action of reprotoxicants upon different types of ncRNAs and epigenetic modifications causing transgenerationally transmitted characters through germ cells but affecting germ cells and reproductive systems. A functional model of epigenetic mechanisms of transgenerational transmission ncRNAs-mediated is also proposed. PMID:27023531

  20. A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear.

    PubMed

    Schrauwen, Isabelle; Hasin-Brumshtein, Yehudit; Corneveaux, Jason J; Ohmen, Jeffrey; White, Cory; Allen, April N; Lusis, Aldons J; Van Camp, Guy; Huentelman, Matthew J; Friedman, Rick A

    2016-03-01

    The mammalian inner ear consists of the cochlea and the vestibular labyrinth (utricle, saccule, and semicircular canals), which participate in both hearing and balance. Proper development and life-long function of these structures involves a highly complex coordinated system of spatial and temporal gene expression. The characterization of the inner ear transcriptome is likely important for the functional study of auditory and vestibular components, yet, primarily due to tissue unavailability, detailed expression catalogues of the human inner ear remain largely incomplete. We report here, for the first time, comprehensive transcriptome characterization of the adult human cochlea, ampulla, saccule and utricle of the vestibule obtained from patients without hearing abnormalities. Using RNA-Seq, we measured the expression of >50,000 predicted genes corresponding to approximately 200,000 transcripts, in the adult inner ear and compared it to 32 other human tissues. First, we identified genes preferentially expressed in the inner ear, and unique either to the vestibule or cochlea. Next, we examined expression levels of specific groups of potentially interesting RNAs, such as genes implicated in hearing loss, long non-coding RNAs, pseudogenes and transcripts subject to nonsense mediated decay (NMD). We uncover the spatial specificity of expression of these RNAs in the hearing/balance system, and reveal evidence of tissue specific NMD. Lastly, we investigated the non-syndromic deafness loci to which no gene has been mapped, and narrow the list of potential candidates for each locus. These data represent the first high-resolution transcriptome catalogue of the adult human inner ear. A comprehensive identification of coding and non-coding RNAs in the inner ear will enable pathways of auditory and vestibular function to be further defined in the study of hearing and balance. Expression data are freely accessible at https://www.tgen.org/home/research

  1. Transcriptator: An Automated Computational Pipeline to Annotate Assembled Reads and Identify Non Coding RNA

    PubMed Central

    Zuccaro, Antonio; Guarracino, Mario Rosario

    2015-01-01

    RNA-seq is a new tool to measure RNA transcript counts, using high-throughput sequencing at an extraordinary accuracy. It provides quantitative means to explore the transcriptome of an organism of interest. However, interpreting this extremely large data into biological knowledge is a problem, and biologist-friendly tools are lacking. In our lab, we developed Transcriptator, a web application based on a computational Python pipeline with a user-friendly Java interface. This pipeline uses the web services available for BLAST (Basis Local Search Alignment Tool), QuickGO and DAVID (Database for Annotation, Visualization and Integrated Discovery) tools. It offers a report on statistical analysis of functional and Gene Ontology (GO) annotation’s enrichment. It helps users to identify enriched biological themes, particularly GO terms, pathways, domains, gene/proteins features and protein—protein interactions related informations. It clusters the transcripts based on functional annotations and generates a tabular report for functional and gene ontology annotations for each submitted transcript to the web server. The implementation of QuickGo web-services in our pipeline enable the users to carry out GO-Slim analysis, whereas the integration of PORTRAIT (Prediction of transcriptomic non coding RNA (ncRNA) by ab initio methods) helps to identify the non coding RNAs and their regulatory role in transcriptome. In summary, Transcriptator is a useful software for both NGS and array data. It helps the users to characterize the de-novo assembled reads, obtained from NGS experiments for non-referenced organisms, while it also performs the functional enrichment analysis of differentially expressed transcripts/genes for both RNA-seq and micro-array experiments. It generates easy to read tables and interactive charts for better understanding of the data. The pipeline is modular in nature, and provides an opportunity to add new plugins in the future. Web application is freely

  2. CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC

    SciTech Connect

    Congrains, Ada; Kamide, Kei; Katsuya, Tomohiro; Yasuda, Osamu; Oguro, Ryousuke; Yamamoto, Koichi; Ohishi, Mitsuru; Rakugi, Hiromi

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer ANRIL maps in the strongest susceptibility locus for cardiovascular disease. Black-Right-Pointing-Pointer Silencing of ANRIL leads to altered expression of tissue remodeling-related genes. Black-Right-Pointing-Pointer The effects of ANRIL on gene expression are splicing variant specific. Black-Right-Pointing-Pointer ANRIL affects progression of cardiovascular disease by regulating proliferation and apoptosis pathways. -- Abstract: ANRIL is a newly discovered non-coding RNA lying on the strongest genetic susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21 region. Genome-wide association studies have been linking polymorphisms in this locus with CVD and several other major diseases such as diabetes and cancer. The role of this non-coding RNA in atherosclerosis progression is still poorly understood. In this study, we investigated the implication of ANRIL in the modulation of gene sets directly involved in atherosclerosis. We designed and tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of the transcript and successfully knocked down expression of ANRIL in human aortic vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array to profile gene expression changes caused by ANRIL knock down. Notably, the genes affected by each of the siRNAs were different, suggesting that different splicing variants of ANRIL might have distinct roles in cell physiology. Our results suggest that ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies.

  3. An Interactive network of long non-coding RNAs facilitates the Drosophila sex determination decision

    PubMed Central

    Mulvey, Brett B.; Olcese, Ursula; Cabrera, Janel R.; Horabin, Jamila I.

    2014-01-01

    Genome analysis in several eukaryotes shows a surprising number of transcripts which do not encode conventional messenger RNAs. Once considered noise, these non-coding RNAs (ncRNAs) appear capable of controlling gene expression by various means. We find Drosophila sex determination, specifically the master-switch gene Sex-lethal (Sxl), is regulated by long ncRNAs (>200 nt). The lncRNAs influence the dose sensitive establishment promoter of Sxl, SxlPe, which must be activated to specify female sex. They are primarily from two regions, R1 and R2, upstream of SxlPeand show a dynamic developmental profile. Of the four lncRNA strands only one, R2 antisense, has its peak coincident with SxlPe transcription, suggesting it may promote activation. Indeed, its expression is regulated by the X chromosome counting genes, whose dose determines whether SxlPe is transcribed. Transgenic lines which ectopically express each of the lncRNAs show they can act in trans, impacting the process of sex determination but also altering the levels of the other lncRNAs. Generally, expression of R1 is negative whereas R2 is positive to females. This ectopic expression also results in a change in the local chromatin marks, affecting the timing and strength of SxlPe transcription. The chromatin marks are those deposited by the Polycomb and Trithorax groups of chromatin modifying proteins, which we find bind to the lncRNAs. We suggest the increasing numbers of non-coding transcripts being identified are a harbinger of interacting networks similar to the one we describe. PMID:24954180

  4. Non-coding RNAs: Epigenetic regulators of bone development and homeostasis.

    PubMed

    Hassan, Mohammad Q; Tye, Coralee E; Stein, Gary S; Lian, Jane B

    2015-12-01

    Non-coding RNAs (ncRNAs) have evolved in eukaryotes as epigenetic regulators of gene expression. The most abundant regulatory ncRNAs are the 20-24 nt small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs, <200 nt). Each class of ncRNAs operates through distinct mechanisms, but their pathways to regulating gene expression are interrelated in ways that are just being recognized. While the importance of lncRNAs in epigenetic control of transcription, developmental processes and human traits is emerging, the identity of lncRNAs in skeletal biology is scarcely known. However, since the first profiling studies of miRNA at stages during osteoblast and osteoclast differentiation, over 1100 publications related to bone biology and pathologies can be found, as well as many recent comprehensive reviews summarizing miRNA in skeletal cells. Delineating the activities and targets of specific miRNAs regulating differentiation of osteogenic and resorptive bone cells, coupled with in vivo gain- and loss-of-function studies, discovered unique mechanisms that support bone development and bone homeostasis in adults. We present here "guiding principles" for addressing biological control of bone tissue formation by ncRNAs. This review emphasizes recent advances in understanding regulation of the process of miRNA biogenesis that impact on osteogenic lineage commitment, transcription factors and signaling pathways. Also discussed are the approaches to be pursued for an understanding of the role of lncRNAs in bone and the challenges in addressing their multiple and complex functions. Based on new knowledge of epigenetic control of gene expression to be gained for ncRNA regulation of the skeleton, new directions for translating the miRNAs and lncRNAs into therapeutic targets for skeletal disorders are possible. This article is part of a Special Issue entitled Epigenetics and Bone. PMID:26039869

  5. Non-coding RNAs Enabling Prognostic Stratification and Prediction of Therapeutic Response in Colorectal Cancer Patients.

    PubMed

    Perakis, Samantha O; Thomas, Joseph E; Pichler, Martin

    2016-01-01

    Colorectal cancer (CRC) is a heterogeneous disease and current treatment options for patients are associated with a wide range of outcomes and tumor responses. Although the traditional TNM staging system continues to serve as a crucial tool for estimating CRC prognosis and for stratification of treatment choices and long-term survival, it remains limited as it relies on macroscopic features and cases of surgical resection, fails to incorporate new molecular data and information, and cannot perfectly predict the variety of outcomes and responses to treatment associated with tumors of the same stage. Although additional histopathologic features have recently been applied in order to better classify individual tumors, the future might incorporate the use of novel molecular and genetic markers in order to maximize therapeutic outcome and to provide accurate prognosis. Such novel biomarkers, in addition to individual patient tumor phenotyping and other validated genetic markers, could facilitate the prediction of risk of progression in CRC patients and help assess overall survival. Recent findings point to the emerging role of non-protein-coding regions of the genome in their contribution to the progression of cancer and tumor formation. Two major subclasses of non-coding RNAs (ncRNAs), microRNAs and long non-coding RNAs, are often dysregulated in CRC and have demonstrated their diagnostic and prognostic potential as biomarkers. These ncRNAs are promising molecular classifiers and could assist in the stratification of patients into appropriate risk groups to guide therapeutic decisions and their expression patterns could help determine prognosis and predict therapeutic options in CRC. PMID:27573901

  6. DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts.

    PubMed

    Paraskevopoulou, Maria D; Vlachos, Ioannis S; Karagkouni, Dimitra; Georgakilas, Georgios; Kanellos, Ilias; Vergoulis, Thanasis; Zagganas, Konstantinos; Tsanakas, Panayiotis; Floros, Evangelos; Dalamagas, Theodore; Hatzigeorgiou, Artemis G

    2016-01-01

    microRNAs (miRNAs) are short non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of coding gene expression. Long non-coding RNAs (lncRNAs) have been recently reported to interact with miRNAs. The sponge-like function of lncRNAs introduces an extra layer of complexity in the miRNA interactome. DIANA-LncBase v1 provided a database of experimentally supported and in silico predicted miRNA Recognition Elements (MREs) on lncRNAs. The second version of LncBase (www.microrna.gr/LncBase) presents an extensive collection of miRNA:lncRNA interactions. The significantly enhanced database includes more than 70 000 low and high-throughput, (in)direct miRNA:lncRNA experimentally supported interactions, derived from manually curated publications and the analysis of 153 AGO CLIP-Seq libraries. The new experimental module presents a 14-fold increase compared to the previous release. LncBase v2 hosts in silico predicted miRNA targets on lncRNAs, identified with the DIANA-microT algorithm. The relevant module provides millions of predicted miRNA binding sites, accompanied with detailed metadata and MRE conservation metrics. LncBase v2 caters information regarding cell type specific miRNA:lncRNA regulation and enables users to easily identify interactions in 66 different cell types, spanning 36 tissues for human and mouse. Database entries are also supported by accurate lncRNA expression information, derived from the analysis of more than 6 billion RNA-Seq reads. PMID:26612864

  7. A global profile of glucose-sensitive endothelial-expressed long non-coding RNAs.

    PubMed

    Singh, Krishna K; Mantella, Laura-Eve; Pan, Yi; Quan, Adrian; Sabongui, Sandra; Sandhu, Paul; Teoh, Hwee; Al-Omran, Mohammed; Verma, Subodh

    2016-09-01

    Hyperglycemia-related endothelial dysfunction is believed to be the crux of diabetes-associated micro- and macro-vascular complications. We conducted a systematic transcriptional survey to screen for human endothelial long non-coding RNAs (lncRNAs) regulated by elevated glucose levels. lncRNAs and protein-coding transcripts from human umbilical vein endothelial cells (HUVECs) cultured under high (25 mmol/L) or normal (5 mmol/L) glucose conditions for 24 h were profiled with the Arraystar Human LncRNA Expression Microarray V3.0. Of the 30 586 lncRNAs screened, 100 were significantly upregulated and 186 appreciably downregulated (P < 0.05) in response to high-glucose exposure. In the same HUVEC samples, 133 of the 26 109 mRNAs screened were upregulated and 166 downregulated. Of these 299 differentially expressed mRNAs, 26 were significantly associated with 28 differentially expressed long intergenic non-coding RNAs (P < 0.05). Bioinformatics analyses indicated that the mRNAs most upregulated are primarily enriched in axon guidance signaling pathways; those most downregulated are notably involved in pathways targeting vascular smooth muscle cell contraction, dopaminergic signaling, ubiquitin-mediated proteolysis, and adrenergic signaling. This is the first lncRNA and mRNA transcriptome profile of high-glucose-mediated changes in human endothelial cells. These observations may prove novel insights into novel regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction and, accordingly, diabetes-associated vascular disease. PMID:27434139

  8. An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes and Non-Coding Transcripts

    PubMed Central

    Hoeppner, Marc P.; Lundquist, Andrew; Pirun, Mono; Meadows, Jennifer R. S.; Zamani, Neda; Johnson, Jeremy; Sundström, Görel; Cook, April; FitzGerald, Michael G.; Swofford, Ross; Mauceli, Evan; Moghadam, Behrooz Torabi; Greka, Anna; Alföldi, Jessica; Abouelleil, Amr; Aftuck, Lynne; Bessette, Daniel; Berlin, Aaron; Brown, Adam; Gearin, Gary; Lui, Annie; Macdonald, J. Pendexter; Priest, Margaret; Shea, Terrance; Turner-Maier, Jason; Zimmer, Andrew; Lander, Eric S.; di Palma, Federica

    2014-01-01

    The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog ∼175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional ∼3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to ∼20,700 high-confidence protein coding loci, we found ∼4,600 antisense transcripts overlapping exons of protein coding genes, ∼7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and ∼11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts. PMID:24625832

  9. DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts

    PubMed Central

    Paraskevopoulou, Maria D.; Vlachos, Ioannis S.; Karagkouni, Dimitra; Georgakilas, Georgios; Kanellos, Ilias; Vergoulis, Thanasis; Zagganas, Konstantinos; Tsanakas, Panayiotis; Floros, Evangelos; Dalamagas, Theodore; Hatzigeorgiou, Artemis G.

    2016-01-01

    microRNAs (miRNAs) are short non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of coding gene expression. Long non-coding RNAs (lncRNAs) have been recently reported to interact with miRNAs. The sponge-like function of lncRNAs introduces an extra layer of complexity in the miRNA interactome. DIANA-LncBase v1 provided a database of experimentally supported and in silico predicted miRNA Recognition Elements (MREs) on lncRNAs. The second version of LncBase (www.microrna.gr/LncBase) presents an extensive collection of miRNA:lncRNA interactions. The significantly enhanced database includes more than 70 000 low and high-throughput, (in)direct miRNA:lncRNA experimentally supported interactions, derived from manually curated publications and the analysis of 153 AGO CLIP-Seq libraries. The new experimental module presents a 14-fold increase compared to the previous release. LncBase v2 hosts in silico predicted miRNA targets on lncRNAs, identified with the DIANA-microT algorithm. The relevant module provides millions of predicted miRNA binding sites, accompanied with detailed metadata and MRE conservation metrics. LncBase v2 caters information regarding cell type specific miRNA:lncRNA regulation and enables users to easily identify interactions in 66 different cell types, spanning 36 tissues for human and mouse. Database entries are also supported by accurate lncRNA expression information, derived from the analysis of more than 6 billion RNA-Seq reads. PMID:26612864

  10. Transcriptator: An Automated Computational Pipeline to Annotate Assembled Reads and Identify Non Coding RNA.

    PubMed

    Tripathi, Kumar Parijat; Evangelista, Daniela; Zuccaro, Antonio; Guarracino, Mario Rosario

    2015-01-01

    RNA-seq is a new tool to measure RNA transcript counts, using high-throughput sequencing at an extraordinary accuracy. It provides quantitative means to explore the transcriptome of an organism of interest. However, interpreting this extremely large data into biological knowledge is a problem, and biologist-friendly tools are lacking. In our lab, we developed Transcriptator, a web application based on a computational Python pipeline with a user-friendly Java interface. This pipeline uses the web services available for BLAST (Basis Local Search Alignment Tool), QuickGO and DAVID (Database for Annotation, Visualization and Integrated Discovery) tools. It offers a report on statistical analysis of functional and Gene Ontology (GO) annotation's enrichment. It helps users to identify enriched biological themes, particularly GO terms, pathways, domains, gene/proteins features and protein-protein interactions related informations. It clusters the transcripts based on functional annotations and generates a tabular report for functional and gene ontology annotations for each submitted transcript to the web server. The implementation of QuickGo web-services in our pipeline enable the users to carry out GO-Slim analysis, whereas the integration of PORTRAIT (Prediction of transcriptomic non coding RNA (ncRNA) by ab initio methods) helps to identify the non coding RNAs and their regulatory role in transcriptome. In summary, Transcriptator is a useful software for both NGS and array data. It helps the users to characterize the de-novo assembled reads, obtained from NGS experiments for non-referenced organisms, while it also performs the functional enrichment analysis of differentially expressed transcripts/genes for both RNA-seq and micro-array experiments. It generates easy to read tables and interactive charts for better understanding of the data. The pipeline is modular in nature, and provides an opportunity to add new plugins in the future. Web application is freely

  11. A Dual Model for Prioritizing Cancer Mutations in the Non-coding Genome Based on Germline and Somatic Events

    PubMed Central

    Li, Jia; Poursat, Marie-Anne; Drubay, Damien; Motz, Arnaud; Saci, Zohra; Morillon, Antonin; Michiels, Stefan; Gautheret, Daniel

    2015-01-01

    We address here the issue of prioritizing non-coding mutations in the tumoral genome. To this aim, we created two independent computational models. The first (germline) model estimates purifying selection based on population SNP data. The second (somatic) model estimates tumor mutation density based on whole genome tumor sequencing. We show that each model reflects a different set of constraints acting either on the normal or tumor genome, and we identify the specific genome features that most contribute to these constraints. Importantly, we show that the somatic mutation model carries independent functional information that can be used to narrow down the non-coding regions that may be relevant to cancer progression. On this basis, we identify positions in non-coding RNAs and the non-coding parts of mRNAs that are both under purifying selection in the germline and protected from mutation in tumors, thus introducing a new strategy for future detection of cancer driver elements in the expressed non-coding genome. PMID:26588488

  12. Low-cost production of green microalga Botryococcus braunii biomass with high lipid content through mixotrophic and photoautotrophic cultivation.

    PubMed

    Yeesang, Chittra; Cheirsilp, Benjamas

    2014-09-01

    Botryococcus braunii is a microalga that is regarded as a potential source of renewable fuel because of its ability to produce large amounts of lipid that can be converted into biodiesel. Agro-industrial by-products and wastes are of great interest as cultivation medium for microorganisms because of their low cost, renewable nature, and abundance. In this study, two strategies for low-cost production of B. braunii biomass with high lipid content were performed: (i) the mixotrophic cultivation using molasses, a cheap by-product from the sugar cane plant as a carbon source, and (ii) the photoautotrophic cultivation using nitrate-rich wastewater supplemented with CO2 as a carbon source. The mixotrophic cultivation added with 15 g L(-1) molasses produced a high amount of biomass of 3.05 g L(-1) with a high lipid content of 36.9 %. The photoautotrophic cultivation in nitrate-rich wastewater supplemented with 2.0 % CO2 produced a biomass of 2.26 g L(-1) and a lipid content of 30.3 %. The benefits of this photoautotrophic cultivation are that this cultivation would help to reduce accumulation of atmospheric carbon dioxide and more than 90 % of the nitrate could be removed from the wastewater. When this cultivation was scaled up in a stirred tank photobioreactor and run with semi-continuous cultivation regime, the highest microalgal biomass of 5.16 g L(-1) with a comparable lipid content of 32.2 % was achieved. These two strategies could be promising ways for producing cheap lipid-rich microalgal biomass that can be used as biofuel feedstocks and animal feeds. PMID:24989454

  13. The fusion of two worlds: non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications (Review).

    PubMed

    Sato-Kuwabara, Yukie; Melo, Sonia A; Soares, Fernando A; Calin, George A

    2015-01-01

    The role of the extracellular non-coding RNAs, particularly microRNAs present in tumor-derived extravesicles, has been intensively exploited in human cancer as a promising tool for diagnostic and prognostic purposes. Current knowledge on exosomes shows an important role not only as vehicles in the intercellular communication, but the transfer of their content can specifically modulate the surrounding microenvironment, leading to tumor development and progression and affecting therapy response. Based on this, much effort has focused on understanding the mechanisms behind the biology of exosomes and their closely interaction with non-coding RNAs as an efficient tool in tumor diagnostic and therapy. Here we summarize the current knowledge on extracellular and exosomes-enclosed non-coding RNAs, and their importance as potential biomarkers and mediators of intercellular communication in tumor biology. PMID:25338714

  14. Supporting data for characterization of non-coding RNAs associated with the Neuronal growth regulator 1 (NEGR1) adhesion protein.

    PubMed

    Kaur, Prameet; Tan, Jun Rong; Karolina, Dwi Setyowati; Sepramaniam, Sugunavathi; Armugam, Arunmozhiarasi; Peter Wong, Tsun-Hon; Jeyaseelan, Kandiah

    2016-06-01

    Long non-coding RNAs and microRNAs control gene expression to determine central nervous system development and function. Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule that plays an important role in neurite outgrowth during neuronal development and its precise expression is crucial for correct brain development. The data described here is related to the research article titled "A long non-coding RNA, BC048612 and a microRNA, miR-203 coordinate the gene expression of Neuronal growth regulator 1 (NEGR1) adhesion protein" [1]. This data article contains detailed bioinformatics analysis of genetic signatures at the Negr1 gene locus retrieved from the UCSC genome browser. This approach could be adopted to identify putative regulatory non-coding RNAs in other tissues and diseases. PMID:26977442

  15. OncodriveFML: a general framework to identify coding and non-coding regions with cancer driver mutations.

    PubMed

    Mularoni, Loris; Sabarinathan, Radhakrishnan; Deu-Pons, Jordi; Gonzalez-Perez, Abel; López-Bigas, Núria

    2016-01-01

    Distinguishing the driver mutations from somatic mutations in a tumor genome is one of the major challenges of cancer research. This challenge is more acute and far from solved for non-coding mutations. Here we present OncodriveFML, a method designed to analyze the pattern of somatic mutations across tumors in both coding and non-coding genomic regions to identify signals of positive selection, and therefore, their involvement in tumorigenesis. We describe the method and illustrate its usefulness to identify protein-coding genes, promoters, untranslated regions, intronic splice regions, and lncRNAs-containing driver mutations in several malignancies. PMID:27311963

  16. Non-coding yet non-trivial: a review on the computational genomics of lincRNAs.

    PubMed

    Ching, Travers; Masaki, Jayson; Weirather, Jason; Garmire, Lana X

    2015-01-01

    Long intergenic non-coding RNAs (lincRNAs) represent one of the most mysterious RNA species encoded by the human genome. Thanks to next generation sequencing (NGS) technology and its applications, we have recently witnessed a surge in non-coding RNA research, including lincRNA research. Here, we summarize the recent advancement in genomics studies of lincRNAs. We review the emerging characteristics of lincRNAs, the experimental and computational approaches to identify lincRNAs, their known mechanisms of regulation, the computational methods and resources for lincRNA functional predictions, and discuss the challenges to understanding lincRNA comprehensively. PMID:26697116

  17. Multifractal detrended cross-correlation analysis of coding and non-coding DNA sequences through chaos-game representation

    NASA Astrophysics Data System (ADS)

    Pal, Mayukha; Satish, B.; Srinivas, K.; Rao, P. Madhusudana; Manimaran, P.

    2015-10-01

    We propose a new approach combining the chaos game representation and the two dimensional multifractal detrended cross correlation analysis methods to examine multifractal behavior in power law cross correlation between any pair of nucleotide sequences of unequal lengths. In this work, we analyzed the characteristic behavior of coding and non-coding DNA sequences of eight prokaryotes. The results show the presence of strong multifractal nature between coding and non-coding sequences of all data sets. We found that this integrative approach helps us to consider complete DNA sequences for characterization, and further it may be useful for classification, clustering, identification of class affiliation of nucleotide sequences etc. with high precision.

  18. Long non-coding RNA containing ultraconserved genomic region 8 promotes bladder cancer tumorigenesis.

    PubMed

    Olivieri, Michele; Ferro, Matteo; Terreri, Sara; Durso, Montano; Romanelli, Alessandra; Avitabile, Concetta; De Cobelli, Ottavio; Messere, Anna; Bruzzese, Dario; Vannini, Ivan; Marinelli, Luciana; Novellino, Ettore; Zhang, Wei; Incoronato, Mariarosaria; Ilardi, Gennaro; Staibano, Stefania; Marra, Laura; Franco, Renato; Perdonà, Sisto; Terracciano, Daniela; Czerniak, Bogdan; Liguori, Giovanna L; Colonna, Vincenza; Fabbri, Muller; Febbraio, Ferdinando; Calin, George A; Cimmino, Amelia

    2016-04-12

    Ultraconserved regions (UCRs) have been shown to originate non-coding RNA transcripts (T-UCRs) that have different expression profiles and play functional roles in the pathophysiology of multiple cancers. The relevance of these functions to the pathogenesis of bladder cancer (BlCa) is speculative. To elucidate this relevance, we first used genome-wide profiling to evaluate the expression of T-UCRs in BlCa tissues. Analysis of two datasets comprising normal bladder tissues and BlCa specimens with a custom T-UCR microarray identified ultraconserved RNA (uc.) 8+ as the most upregulated T-UCR in BlCa tissues, although its expression was lower than in pericancerous bladder tissues. These results were confirmed on BlCa tissues by real-time PCR and by in situ hybridization. Although uc.8+ is located within intron 1 of CASZ1, a zinc-finger transcription factor, the transcribed non-coding RNA encoding uc.8+ is expressed independently of CASZ1. In vitro experiments evaluating the effects of uc.8+ silencing, showed significantly decreased capacities for cancer cell invasion, migration, and proliferation. From this, we proposed and validated a model of interaction in which uc.8+ shuttles from the nucleus to the cytoplasm of BlCa cells, interacts with microRNA (miR)-596, and cooperates in the promotion and development of BlCa. Using computational analysis, we investigated the miR-binding domain accessibility, as determined by base-pairing interactions within the uc.8+ predicted secondary structure, RNA binding affinity, and RNA species abundance in bladder tissues and showed that uc.8+ is a natural decoy for miR-596. Thus uc.8+ upregulation results in increased expression of MMP9, increasing the invasive potential of BlCa cells. These interactions between evolutionarily conserved regions of DNA suggest that natural selection has preserved this potentially regulatory layer that uses RNA to modulate miR levels, opening up the possibility for development of useful markers for

  19. Long non-coding RNA containing ultraconserved genomic region 8 promotes bladder cancer tumorigenesis

    PubMed Central

    Durso, Montano; Romanelli, Alessandra; Avitabile, Concetta; De Cobelli, Ottavio; Messere, Anna; Bruzzese, Dario; Vannini, Ivan; Marinelli, Luciana; Novellino, Ettore; Zhang, Wei; Incoronato, Mariarosaria; Ilardi, Gennaro; Staibano, Stefania; Marra, Laura; Franco, Renato; Perdonà, Sisto; Terracciano, Daniela; Czerniak, Bogdan; Liguori, Giovanna L.; Colonna, Vincenza; Fabbri, Muller; Febbraio, Ferdinando

    2016-01-01

    Ultraconserved regions (UCRs) have been shown to originate non-coding RNA transcripts (T-UCRs) that have different expression profiles and play functional roles in the pathophysiology of multiple cancers. The relevance of these functions to the pathogenesis of bladder cancer (BlCa) is speculative. To elucidate this relevance, we first used genome-wide profiling to evaluate the expression of T-UCRs in BlCa tissues. Analysis of two datasets comprising normal bladder tissues and BlCa specimens with a custom T-UCR microarray identified ultraconserved RNA (uc.) 8+ as the most upregulated T-UCR in BlCa tissues, although its expression was lower than in pericancerous bladder tissues. These results were confirmed on BlCa tissues by real-time PCR and by in situ hybridization. Although uc.8+ is located within intron 1 of CASZ1, a zinc-finger transcription factor, the transcribed non-coding RNA encoding uc.8+ is expressed independently of CASZ1. In vitro experiments evaluating the effects of uc.8+ silencing, showed significantly decreased capacities for cancer cell invasion, migration, and proliferation. From this, we proposed and validated a model of interaction in which uc.8+ shuttles from the nucleus to the cytoplasm of BlCa cells, interacts with microRNA (miR)-596, and cooperates in the promotion and development of BlCa. Using computational analysis, we investigated the miR-binding domain accessibility, as determined by base-pairing interactions within the uc.8+ predicted secondary structure, RNA binding affinity, and RNA species abundance in bladder tissues and showed that uc.8+ is a natural decoy for miR-596. Thus uc.8+ upregulation results in increased expression of MMP9, increasing the invasive potential of BlCa cells. These interactions between evolutionarily conserved regions of DNA suggest that natural selection has preserved this potentially regulatory layer that uses RNA to modulate miR levels, opening up the possibility for development of useful markers for

  20. Integrative Analysis of Normal Long Intergenic Non-Coding RNAs in Prostate Cancer.

    PubMed

    Bawa, Pushpinder; Zackaria, Sajna; Verma, Mohit; Gupta, Saurabh; Srivatsan, R; Chaudhary, Bibha; Srinivasan, Subhashini

    2015-01-01

    Recently, large numbers of normal human tissues have been profiled for non-coding RNAs and more than fourteen thousand long intergenic non-coding RNAs (lincRNAs) are found expressed in normal human tissues. The functional roles of these normal lincRNAs (nlincRNAs) in the regulation of protein coding genes in normal and disease biology are yet to be established. Here, we have profiled two RNA-seq datasets including cancer and matched non-neoplastic tissues from 12 individuals from diverse demography for both coding genes and nlincRNAs. We find 130 nlincRNAs significantly regulated in cancer, with 127 regulated in the same direction in the two datasets. Interestingly, according to Illumina Body Map, significant numbers of these nlincRNAs display baseline null expression in normal prostate tissues but are specific to other tissues such as thyroid, kidney, liver and testis. A number of the regulated nlincRNAs share loci with coding genes, which are either co-regulated or oppositely regulated in all cancer samples studied here. For example, in all cancer samples i) the nlincRNA, TCONS_00029157, and a neighboring tumor suppressor factor, SIK1, are both down regulated; ii) several thyroid-specific nlincRNAs in the neighborhood of the thyroid-specific gene TPO, are both up-regulated; and iii) the TCONS_00010581, an isoform of HEIH, is down-regulated while the neighboring EZH2 gene is up-regulated in cancer. Several nlincRNAs from a prostate cancer associated chromosomal locus, 8q24, are up-regulated in cancer along with other known prostate cancer associated genes including PCAT-1, PVT1, and PCAT-92. We observe that there is significant bias towards up-regulation of nlincRNAs with as high as 118 out of 127 up-regulated in cancer, even though regulation of coding genes is skewed towards down-regulation. Considering that all reported cancer associated lincRNAs (clincRNAs) are biased towards up-regulation, we conclude that this bias may be functionally relevant. PMID:25933431

  1. Natural variation in non-coding regions underlying phenotypic diversity in budding yeast.

    PubMed

    Salinas, Francisco; de Boer, Carl G; Abarca, Valentina; García, Verónica; Cuevas, Mara; Araos, Sebastian; Larrondo, Luis F; Martínez, Claudio; Cubillos, Francisco A

    2016-01-01

    Linkage mapping studies in model organisms have typically focused their efforts in polymorphisms within coding regions, ignoring those within regulatory regions that may contribute to gene expression variation. In this context, differences in transcript abundance are frequently proposed as a source of phenotypic diversity between individuals, however, until now, little molecular evidence has been provided. Here, we examined Allele Specific Expression (ASE) in six F1 hybrids from Saccharomyces cerevisiae derived from crosses between representative strains of the four main lineages described in yeast. ASE varied between crosses with levels ranging between 28% and 60%. Part of the variation in expression levels could be explained by differences in transcription factors binding to polymorphic cis-regulations and to differences in trans-activation depending on the allelic form of the TF. Analysis on highly expressed alleles on each background suggested ASN1 as a candidate transcript underlying nitrogen consumption differences between two strains. Further promoter allele swap analysis under fermentation conditions confirmed that coding and non-coding regions explained aspartic and glutamic acid consumption differences, likely due to a polymorphism affecting Uga3 binding. Together, we provide a new catalogue of variants to bridge the gap between genotype and phenotype. PMID:26898953

  2. Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction.

    PubMed

    Shan, K; Jiang, Q; Wang, X-Q; Wang, Y-N-Z; Yang, H; Yao, M-D; Liu, C; Li, X-M; Yao, J; Liu, B; Zhang, Y-Y; J, Yong; Yan, B

    2016-01-01

    Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. Long non-coding RNAs (lncRNAs) have been implicated in several biological processes and human diseases. Here we show that lncRNA-RNCR3 is expressed in ECs and VSMCs. RNCR3 expression is significantly upregulated in mouse and human aortic atherosclerotic lesions, and cultured ECs and VSMCs upon ox-LDL treatment in vitro. RNCR3 knockdown accelerates the development of atherosclerosis, aggravates hypercholesterolemia and inflammatory factor releases, and decreases EC and VSMC proliferation in vivo. RNCR3 knockdown also reduces the proliferation and migration, and accelerates apoptosis development of EC and VSMC in vitro. RNCR3 acts as a ceRNA, and forms a feedback loop with Kruppel-like factor 2 and miR-185-5p to regulate cell function. This study reveals that RNCR3 has an atheroprotective role in atherosclerosis, and its intervention is a promising strategy for treating atherosclerosis-related vascular dysfunction. PMID:27253412

  3. CCAT1: a pivotal oncogenic long non-coding RNA in human cancers.

    PubMed

    Xin, Yu; Li, Zheng; Shen, Jianxiong; Chan, Matthew T V; Wu, William Ka Kei

    2016-06-01

    Long non-coding RNAs (lncRNAs) compose a group of non-protein-coding RNAs - more than 200 nucleotides in length. Recent studies have shown that lncRNAs play important roles in different cellular processes, including proliferation, differentiation, migration and invasion. Deregulation of lncRNAs has been widely reported in human tumours, in which they are able to function as either oncogenes (on the one hand) or tumour suppressor genes (on the other). Deregulation of CCAT1 (colon cancer-associated transcript-1), an oncogenic lncRNA, has been documented in different types of malignancy, such as gastric cancer, colorectal cancer and hepatocellular carcinoma. In this regard, enforced expression of CCAT1 exerts potent tumorigenic effects by promoting cell proliferation, invasion and migration. Recent evidence has also shown that CCAT1 may serve as a prognostic cancer biomarker. In this review, we provide an overview of current evidence relating to the role and biological function of CCAT1 in tumour development. PMID:27134049

  4. Identification of long non-coding RNAs involved in neuronal development and intellectual disability.

    PubMed

    D'haene, Eva; Jacobs, Eva Z; Volders, Pieter-Jan; De Meyer, Tim; Menten, Björn; Vergult, Sarah

    2016-01-01

    Recently, exome sequencing led to the identification of causal mutations in 16-31% of patients with intellectual disability (ID), leaving the underlying cause for many patients unidentified. In this context, the noncoding part of the human genome remains largely unexplored. For many long non-coding RNAs (lncRNAs) a crucial role in neurodevelopment and hence the human brain is anticipated. Here we aimed at identifying lncRNAs associated with neuronal development and ID. Therefore, we applied an integrated genomics approach, harnessing several public epigenetic datasets. We found that the presence of neuron-specific H3K4me3 confers the highest specificity for genes involved in neurodevelopment and ID. Based on the presence of this feature and GWAS hits for CNS disorders, we identified 53 candidate lncRNA genes. Extensive expression profiling on human brain samples and other tissues, followed by Gene Set Enrichment Analysis indicates that at least 24 of these lncRNAs are indeed implicated in processes such as synaptic transmission, nervous system development and neurogenesis. The bidirectional or antisense overlapping orientation relative to multiple coding genes involved in neuronal processes supports these results. In conclusion, we identified several lncRNA genes putatively involved in neurodevelopment and CNS disorders, providing a resource for functional studies. PMID:27319317

  5. Transposable Element Insertions in Long Intergenic Non-Coding RNA Genes

    PubMed Central

    Kannan, Sivakumar; Chernikova, Diana; Rogozin, Igor B.; Poliakov, Eugenia; Managadze, David; Koonin, Eugene V.; Milanesi, Luciano

    2015-01-01

    Transposable elements (TEs) are abundant in mammalian genomes and appear to have contributed to the evolution of their hosts by providing novel regulatory or coding sequences. We analyzed different regions of long intergenic non-coding RNA (lincRNA) genes in human and mouse genomes to systematically assess the potential contribution of TEs to the evolution of the structure and regulation of expression of lincRNA genes. Introns of lincRNA genes contain the highest percentage of TE-derived sequences (TES), followed by exons and then promoter regions although the density of TEs is not significantly different between exons and promoters. Higher frequencies of ancient TEs in promoters and exons compared to introns implies that many lincRNA genes emerged before the split of primates and rodents. The content of TES in lincRNA genes is substantially higher than that in protein-coding genes, especially in exons and promoter regions. A significant positive correlation was detected between the content of TEs and evolutionary rate of lincRNAs indicating that inserted TEs are preferentially fixed in fast-evolving lincRNA genes. These results are consistent with the repeat insertion domains of LncRNAs hypothesis under which TEs have substantially contributed to the origin, evolution, and, in particular, fast functional diversification, of lincRNA genes. PMID:26106594

  6. Noncoder: a web interface for exon array-based detection of long non-coding RNAs

    PubMed Central

    Gellert, Pascal; Ponomareva, Yuliya; Braun, Thomas; Uchida, Shizuka

    2013-01-01

    Due to recent technical developments, a high number of long non-coding RNAs (lncRNAs) have been discovered in mammals. Although it has been shown that lncRNAs are regulated differently among tissues and disease statuses, functions of these transcripts are still unknown in most cases. GeneChip Exon 1.0 ST Arrays (exon arrays) from Affymetrix, Inc. have been used widely to profile genome-wide expression changes and alternative splicing of protein-coding genes. Here, we demonstrate that re-annotation of exon array probes can be used to profile expressions of tens of thousands of lncRNAs. With this annotation, a detailed inspection of lncRNAs and their isoforms is possible. To allow for a general usage to the research community, we developed a user-friendly web interface called ‘noncoder’. By uploading CEL files from exon arrays and with a few mouse clicks and parameter settings, exon array data will be normalized and analysed to identify differentially expressed lncRNAs. Noncoder provides the detailed annotation information of lncRNAs and is equipped with unique features to allow for an efficient search for interesting lncRNAs to be studied further. The web interface is available at http://noncoder.mpi-bn.mpg.de. PMID:23012263

  7. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells

    SciTech Connect

    Shi, Yongguo; Lu, Jianwei; Zhou, Jing; Tan, Xueming; He, Ye; Ding, Jie; Tian, Yun; Wang, Li; Wang, Keming

    2014-04-04

    Highlights: • First, we have shown that upregulated of the Loc554202 in breast cancer tissues. • Second, we demonstrated the function of Loc554202 in breast cancer cell. • Finally, we demonstrated that LOC554202 knockdown could inhibit tumor growth in vivo. - Abstract: Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question, we assay the expression level of lncRNAs–Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis.

  8. Insights into the Regulatory Role of Non-coding RNAs in Cancer Metabolism.

    PubMed

    Beltrán-Anaya, Fredy O; Cedro-Tanda, Alberto; Hidalgo-Miranda, Alfredo; Romero-Cordoba, Sandra L

    2016-01-01

    Cancer represents a complex disease originated from alterations in several genes leading to disturbances in important signaling pathways in tumor biology, favoring heterogeneity that promotes adaptability and pharmacological resistance of tumor cells. Metabolic reprogramming has emerged as an important hallmark of cancer characterized by the presence of aerobic glycolysis, increased glutaminolysis and fatty acid biosynthesis, as well as an altered mitochondrial energy production. The metabolic switches that support energetic requirements of cancer cells are closely related to either activation of oncogenes or down-modulation of tumor-suppressor genes, finally leading to dysregulation of cell proliferation, metastasis and drug resistance signals. Non-coding RNAs (ncRNAs) have emerged as one important kind of molecules that can regulate altered genes contributing, to the establishment of metabolic reprogramming. Moreover, diverse metabolic signals can regulate ncRNA expression and activity at genetic, transcriptional, or epigenetic levels. The regulatory landscape of ncRNAs may provide a new approach for understanding and treatment of different types of malignancies. In this review we discuss the regulatory role exerted by ncRNAs on metabolic enzymes and pathways involved in glucose, lipid, and amino acid metabolism. We also review how metabolic stress conditions and tumoral microenvironment influence ncRNA expression and activity. Furthermore, we comment on the therapeutic potential of metabolism-related ncRNAs in cancer. PMID:27551267

  9. Genome-wide analyses of small non-coding RNAs in streptococci

    PubMed Central

    Patenge, Nadja; Pappesch, Roberto; Khani, Afsaneh; Kreikemeyer, Bernd

    2015-01-01

    Streptococci represent a diverse group of Gram-positive bacteria, which colonize a wide range of hosts among animals and humans. Streptococcal species occur as commensal as well as pathogenic organisms. Many of the pathogenic species can cause severe, invasive infections in their hosts leading to a high morbidity and mortality. The consequence is a tremendous suffering on the part of men and livestock besides the significant financial burden in the agricultural and healthcare sectors. An environmentally stimulated and tightly controlled expression of virulence factor genes is of fundamental importance for streptococcal pathogenicity. Bacterial small non-coding RNAs (sRNAs) modulate the expression of genes involved in stress response, sugar metabolism, surface composition, and other properties that are related to bacterial virulence. Even though the regulatory character is shared by this class of RNAs, variation on the molecular level results in a high diversity of functional mechanisms. The knowledge about the role of sRNAs in streptococci is still limited, but in recent years, genome-wide screens for sRNAs have been conducted in an increasing number of species. Bioinformatics prediction approaches have been employed as well as expression analyses by classical array techniques or next generation sequencing. This review will give an overview of whole genome screens for sRNAs in streptococci with a focus on describing the different methods and comparing their outcome considering sRNA conservation among species, functional similarities, and relevance for streptococcal infection. PMID:26042151

  10. Non-coding RNA regulation in pathogenic bacteria located inside eukaryotic cells

    PubMed Central

    Ortega, Álvaro D.; Quereda, Juan J.; Pucciarelli, M. Graciela; García-del Portillo, Francisco

    2014-01-01

    Intracellular bacterial pathogens have evolved distinct lifestyles inside eukaryotic cells. Some pathogens coexist with the infected cell in an obligate intracellular state, whereas others transit between the extracellular and intracellular environment. Adaptation to these intracellular lifestyles is regulated in both space and time. Non-coding small RNAs (sRNAs) are post-transcriptional regulatory molecules that fine-tune important processes in bacterial physiology including cell envelope architecture, intermediate metabolism, bacterial communication, biofilm formation, and virulence. Recent studies have shown production of defined sRNA species by intracellular bacteria located inside eukaryotic cells. The molecules targeted by these sRNAs and their expression dynamics along the intracellular infection cycle remain, however, poorly characterized. Technical difficulties linked to the isolation of “intact” intracellular bacteria from infected host cells might explain why sRNA regulation in these specialized pathogens is still a largely unexplored field. Transition from the extracellular to the intracellular lifestyle provides an ideal scenario in which regulatory sRNAs are intended to participate; so much work must be done in this direction. This review focuses on sRNAs expressed by intracellular bacterial pathogens during the infection of eukaryotic cells, strategies used with these pathogens to identify sRNAs required for virulence, and the experimental technical challenges associated to this type of studies. We also discuss varied techniques for their potential application to study RNA regulation in intracellular bacterial infections. PMID:25429360