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long intervening noncoding RNA

Binod Aryal, Yajaira Suárez
The endothelial lining can be viewed as the first line of defense against risk factors of vascular disease. Endothelial dysfunction is regarded as an initial event for atherogenesis since defects in vascular integrity and homeostasis are responsible for lipid infiltration and recruitment of monocytes into the vessel wall. Monocytes-turned-macrophages, which possess astounding inflammatory plasticity, perpetuate chronic inflammation and growth of atherosclerotic plaques and, are therefore central for the pathogenesis of atherosclerosis...
March 15, 2018: Vascular Pharmacology
Sabrina Shore, Jordana M Henderson, Anton P McCaffrey
Next-generation small RNA sequencing is a valuable tool which is increasing our knowledge regarding small noncoding RNAs and their function in regulating genetic information. Library preparation protocols for small RNA have thus far been restricted due to higher RNA input requirements (>10 ng), long workflows, and tedious manual gel purifications. Small RNA library preparation methods focus largely on the prevention or depletion of a side product known as adapter dimer that tends to dominate the reaction...
2018: Methods in Molecular Biology
Margarita Schlackow, Takayuki Nojima, Tomas Gomes, Ashish Dhir, Maria Carmo-Fonseca, Nick J Proudfoot
Numerous long intervening noncoding RNAs (lincRNAs) are generated from the mammalian genome by RNA polymerase II (Pol II) transcription. Although multiple functions have been ascribed to lincRNAs, their synthesis and turnover remain poorly characterized. Here, we define systematic differences in transcription and RNA processing between protein-coding and lincRNA genes in human HeLa cells. This is based on a range of nascent transcriptomic approaches applied to different nuclear fractions, including mammalian native elongating transcript sequencing (mNET-seq)...
January 5, 2017: Molecular Cell
Haitao Luo, Dechao Bu, Liang Sun, Shuangsang Fang, Zhiyong Liu, Yi Zhao
RNA-seq technology offers the promise of rapid comprehensive discovery of long intervening noncoding RNAs (lincRNAs). Basic tools such as Tophat and Cufflinks have been widely used for RNA-seq assembly. However, advanced bioinformatics methodologies that allow in-depth analysis of lincRNAs are lacking. Here, we describe a computational protocol that is especially designed for the identification of novel lincRNAs and the prediction of the function. The protocol mainly includes two open-access tools, CNCI and ncFANs...
September 1, 2017: Briefings in Bioinformatics
Wenna Guo, Qiang Wang, Yueping Zhan, Xijia Chen, Qi Yu, Jiawei Zhang, Yi Wang, Xin-Jian Xu, Liucun Zhu
Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. The aim of this study is to identify lncRNA signature that can predict breast cancer patient survival. RNA expression data from 1064 patients were downloaded from The Cancer Genome Atlas project. Cox regression, Kaplan-Meier, and receiver operating characteristic (ROC) analyses were performed to construct a model for predicting the overall survival (OS) of patients and evaluate it. A model consisting of three lncRNA genes (CAT104, LINC01234, and STXBP5-AS1) was identified...
2016: Scientific Reports
Jingqiu Li, Haihua Tian, Jie Yang, Zhaohui Gong
The revolutionary findings in nonprotein-coding part of human genome analysis have revealed a large number of RNA transcripts longer than 200 nucleotides that lack coding protein function, termed long noncoding RNAs (lncRNAs). Recently, accumulating shreds of evidence suggest that lncRNAs are widely distributed in human genome and deeply involved in cellular activities such as cell growth, proliferation, and apoptosis. Generally, lncRNAs regulate cell behaviors by targeting cell cycle-associated cyclins, cyclin-dependent kinases (CDKs), and/or CDK inhibitors...
September 2016: DNA and Cell Biology
Thomas M Aune, Phillip S Crooke, Charles F Spurlock
Long noncoding RNAs are recently discovered regulatory RNA molecules that do not code for proteins but influence a vast array of biologic processes. In vertebrates, the number of long noncoding RNA genes is thought to greatly exceed the number of protein-coding genes. It is also thought that long noncoding RNAs drive the biologic complexity observed in vertebrates compared with that in invertebrates. Evidence of this complexity has been found in the T-lymphocyte compartment of the adaptive immune system. In the present review, we describe our current level of understanding of the expression of specific long or large intergenic or intervening long noncoding RNAs during T-lymphocyte development in the thymus and differentiation in the periphery and highlight the mechanisms of action that specific long noncoding RNAs employ to regulate T-lymphocyte function, both in vitro and in vivo...
January 2016: Journal of Leukocyte Biology
Jeremy E Wilusz
It was long assumed that eukaryotic precursor mRNAs (pre-mRNAs) are almost always spliced to generate a linear mRNA that is subsequently translated to produce a protein. However, it is now clear that thousands of protein-coding genes can be non-canonically spliced to produce circular noncoding RNAs, some of which are expressed at much higher levels than their associated linear mRNAs. How then does the splicing machinery decide whether to generate a linear mRNA or a circular RNA? Recent work has revealed that intronic repetitive elements, including sequences derived from transposons, are critical regulators of this decision...
May 2015: Mobile Genetic Elements
Hengyi Xu, Andrew D L Nelson, Dorothy E Shippen
Long noncoding RNAs (lncRNAs) have emerged as critical factors in many biological processes, but little is known about how their regulatory functions evolved. One of the best-studied lncRNAs is TER, the essential RNA template for telomerase reverse transcriptase. We previously showed that Arabidopsis thaliana harbors three TER isoforms: TER1, TER2 and TER2S. TER1 serves as a canonical telomere template, while TER2 is a novel negative regulator of telomerase activity, induced in response to double-strand breaks (DSBs)...
June 2015: PLoS Genetics
Hadas Hezroni, David Koppstein, Matthew G Schwartz, Alexandra Avrutin, David P Bartel, Igor Ulitsky
The inability to predict long noncoding RNAs from genomic sequence has impeded the use of comparative genomics for studying their biology. Here, we develop methods that use RNA sequencing (RNA-seq) data to annotate the transcriptomes of 16 vertebrates and the echinoid sea urchin, uncovering thousands of previously unannotated genes, most of which produce long intervening noncoding RNAs (lincRNAs). Although in each species, >70% of lincRNAs cannot be traced to homologs in species that diverged >50 million years ago, thousands of human lincRNAs have homologs with similar expression patterns in other species...
May 19, 2015: Cell Reports
Shanxin Zhang, Jiuqiang Han, Dexing Zhong, Ruiling Liu, Jiguang Zheng
Long noncoding RNAs (lncRNAs) play essential regulatory roles in the human cancer genome. Many identified lncRNAs are transcribed by RNA polymerase II in which they are polyadenylated, whereby the long intervening noncoding RNAs (lincRNAs) have been widely used for the researches of lncRNAs. To date, the mechanism of lincRNAs polyadenylation related to cancer is rarely fully understood yet. In this paper, first we reported a comprehensive map of global lincRNAs polyadenylation sites (PASs) in five human cancer genomes; second we proposed a grouping method based on the pattern of genes expression and the manner of alternative polyadenylation (APA); third we investigated the distribution of motifs surrounding PASs...
October 2014: Computational Biology and Chemistry
Matthew D Simon, Stefan F Pinter, Rui Fang, Kavitha Sarma, Michael Rutenberg-Schoenberg, Sarah K Bowman, Barry A Kesner, Verena K Maier, Robert E Kingston, Jeannie T Lee
The Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation (XCI), the process by which mammals compensate for unequal numbers of sex chromosomes. During XCI, Xist coats the future inactive X chromosome (Xi) and recruits Polycomb repressive complex 2 (PRC2) to the X-inactivation centre (Xic). How Xist spreads silencing on a 150-megabases scale is unclear. Here we generate high-resolution maps of Xist binding on the X chromosome across a developmental time course using CHART-seq. In female cells undergoing XCI de novo, Xist follows a two-step mechanism, initially targeting gene-rich islands before spreading to intervening gene-poor domains...
December 19, 2013: Nature
Zhili Liu, Ming Sun, Kaihua Lu, Jing Liu, Meiling Zhang, Weiqin Wu, Wei De, Zhaoxia Wang, Rui Wang
HOTAIR, a long intervening non-coding RNA (lincRNA), associates with the Polycomb Repressive Complex 2 (PRC2) and is reported to reprogram chromatin organization and promote tumor progression. However, little is known about the roles of this gene in the development of chemoresistance phenotype of lung adenocarcinoma (LAD). Thus, we investigated the involvement of HOTAIR in the resistance of LAD cells to cisplatin. In this study, we show that HOTAIR expression was significantly upregulated in cisplatin-resistant A549/DDP cells compared with in parental A549 cells...
2013: PloS One
Igor Ulitsky, David P Bartel
Long intervening noncoding RNAs (lincRNAs) are transcribed from thousands of loci in mammalian genomes and might play widespread roles in gene regulation and other cellular processes. This Review outlines the emerging understanding of lincRNAs in vertebrate animals, with emphases on how they are being identified and current conclusions and questions regarding their genomics, evolution and mechanisms of action.
July 3, 2013: Cell
Darko Gosenca, Ute Gabriel, Annette Steidler, Jens Mayer, Olivia Diem, Philipp Erben, Alice Fabarius, Christine Leib-Mösch, Wolf-Karsten Hofmann, Wolfgang Seifarth
Human endogenous retroviruses (HERV) and related elements account for more than 8% of the human genome and significantly contribute to the human transcriptome by long terminal repeat (LTR) promoter activity. In this context, HERVs are thought to intervene in the expression of adjacent genes by providing regulatory sequences (cis-effect) or via noncoding RNA including natural antisense transcripts. To address the potential impact of HERV activity in urothelial carcinoma, we comparatively analyzed the HERV transcription profiles in paired samples of non-malignant urothelium and urothelial carcinoma derived from 13 patients with bladder cancer by means of a retrovirus-specific microarray (RetroArray)...
2012: PloS One
Jin-Wu Nam, David P Bartel
Thousands of long noncoding RNAs (lncRNAs) have been found in vertebrate animals, a few of which have known biological roles. To better understand the genomics and features of lncRNAs in invertebrates, we used available RNA-seq, poly(A)-site, and ribosome-mapping data to identify lncRNAs of Caenorhabditis elegans. We found 170 long intervening ncRNAs (lincRNAs), which had single- or multiexonic structures that did not overlap protein-coding transcripts, and about sixty antisense lncRNAs (ancRNAs), which were complementary to protein-coding transcripts...
December 2012: Genome Research
Igor Ulitsky, Alena Shkumatava, Calvin H Jan, Hazel Sive, David P Bartel
Thousands of long intervening noncoding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation...
December 23, 2011: Cell
Neil R Smalheiser
A decade ago, RNA interference was proposed to serve as a physiologic means of regulating long-term gene expression in the mammalian brain. However, during the intervening years, this hypothesis appeared to be contradicted by both experimental data and theoretical considerations. More recently, the advent of deep sequencing technology has permitted a re-assessment of this issue. As reviewed here, a large population of small RNAs having features characteristic of endogenous siRNAs are detected within adult mouse hippocampus, which derive from genes involved in synaptic structure and signaling, and which show a significant, though modest (16-22%) up-regulation during olfactory discrimination training...
June 2012: Experimental Neurology
Stacie L Bumgarner, Robin D Dowell, Paula Grisafi, David K Gifford, Gerald R Fink
The identification of specific functional roles for the numerous long noncoding (nc)RNAs found in eukaryotic transcriptomes is currently a matter of intense study amid speculation that these ncRNAs have key regulatory roles. We have identified a pair of cis-interfering ncRNAs in yeast that contribute to the control of variegated gene expression at the FLO11 locus by implementing a regulatory circuit that toggles between two stable states. These capped, polyadenylated ncRNAs are transcribed across the large intergenic region upstream of the FLO11 ORF...
October 27, 2009: Proceedings of the National Academy of Sciences of the United States of America
A M Curatola, M S Nadal, R J Schneider
The 3' noncoding region (NCR) AU-rich element (ARE) selectively confers rapid degradation on many mRNAs via a process requiring translation of the message. The role of cotranslation in destabilization of ARE mRNAs was examined by insertion of translation-blocking stable secondary structure at different sites in test mRNAs containing either the granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE or a control sequence. A strong (-80 kcal/mol [1 kcal = 4.184 kJ]) but not a moderate (-30 kcal/mol) secondary structure prevented destabilization of mRNAs when inserted at any position upstream of the ARE, including in the 3' NCR...
November 1995: Molecular and Cellular Biology
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