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Critical evaluation of the FANTOM3 non-coding rna transcripts

GENOMICS 2009年第3期94卷 169-176页

作者： Nordstrom, Karl J. V. Mirza, Majd A. I. Almen, Markus Sallman Gloriam, David E. Fredriksson, Robert Schioth, Helgi B. Uppsala Univ Dept Neurosci S-75124 Uppsala Sweden

We Studied the genomic positions of 38,129 putative ncrnas from the RIKEN dataset in relation to protein-coding genes. We found that the dataset has 41% sense, 6% antisense, 24% intronic and 29% intergenic transcripts. Interestingly, 17,678 (47%) of the FANTOM3 transcripts were found to potentially be internally primed from longer transcripts. The highest fraction of these transcripts was found among the intronic transcripts and as many as 77% or 6929 intronic transcripts were both internally primed and unspliced. We defined a filtered subset of 8535 transcripts that did not overlap with protein-coding genes, did not contain ORFs longer than 100 residues and were not internally primed. This dataset contains 53% of the FANTOM3 transcripts associated to known ncrna in rnadb and expands previous similar efforts with 6523 novel transcripts. This bioinformatic filtering of the FANTOM3 non-coding dataset has generated a lead dataset of transcripts without signs of being artefacts, providing a suitable dataset for investigation with hybridization-based techniques. (c) 2009 Elsevier Inc. All rights reserved.

关键词： RIKEN FANTOM3 ncrna non-coding rna snorna EST

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A 3′ UTR-derived non-coding rna RibS increases expression of cfa and promotes biofilm formation of Salmonella enterica serovar Typhi

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RESEARCH IN MICROBIOLOGY 2018年第6期169卷 279-288页

作者： Zhao, Xin Liu, Rui Tang, Hao Osei-Adjei, George Xu, Shungao Zhang, Ying Huang, Xinxiang Jiangsu Univ Sch Med Dept Biochem & Mol Biol Zhenjiang 212013 Jiangsu Peoples R China

Bacterial non-coding rnas (ncrnas) are widely studied and found to play important roles in regulating various cellular processes. Recently, many ncrnas have been discovered to be transcribed or processed from 3' untranslated regions (3' UTRs). Here we reported a novel 3' UTR-derived ncrna, RibS, which could influence biofilm formation of Salmonella enterica serovar Typhi (S. Typhi). RibS was confirmed to be a similar to 700 nt processed product produced by rnase III-catalyzed cleavage from the 3' UTR of riboflavin synthase subunit alpha mrna, RibE. Overexpression of RibS increased the expression of the cyclopropane fatty acid synthase gene, cfa, which was located at the antisense strand. Biofilm formation of S. Typhi was enhanced by overexpressing RibS both in the wild type strain and cfa deletion mutant. Deletion of cfa attenuated biofilm formation of S. Typhi, while complementation of cfa partly restored the phenotype. Moreover, overexpressing cfa enhanced the biofilm formation of S. Typhi. In summary, RibS has been identified as a novel ncrna derived from the 3' UTR of RibE that promotes biofilm formation of S. Typhi, and it appears to do so, at least in part, by increasing the expression of cfa. (C) 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

关键词： Salmonella enterica serovar Typhi non-coding rna RibS cfa Biofilm

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A long non-coding rna, BC048612 and a microrna, miR-203 coordinate the gene expression of neuronal growth regulator 1 (NEGR1) adhesion protein

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2016年第4期1863卷 533-543页

作者： Kaur, Prameet Tan, Jun Rong Karolina, Dwi Setyowati Sepramaniam, Sugunavathi Armugam, Arunmozhiarasi Wong, Peter T-H Jeyaseelan, Kandiah Natl Univ Singapore Dept Biochem Yong Loo Lin Sch Med 8 Med Dr Singapore 117597 Singapore Natl Univ Singapore Dept Pharmacol Yong Loo Lin Sch Med 10 Med Dr Singapore 117597 Singapore Monash Univ Dept Anat & Dev Biol Sch Biomed Sci Fac Med Nursing & Hlth Sci Clayton Vic 3800 Australia

The regulatory roles for non-coding rnas, the long non-coding rnas and micrornas, are emerging as crucial determinants of central nervous system development and function. Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule that has been shown to play an important role in neurite outgrowth during neuronal development. Precise expression of the Negr1 gene is crucial for proper brain development and is dysregulated during brain injury. Hence, we attempted to elucidate the non-coding rnas that control Negr1 gene expression. A long non-coding rna, BC048612, transcribed from the bidirectional GC-rich Negr1 gene promoter was found to influence Negr1 mrna expression. In vitro knockdown of the long non-coding rna resulted in significant down-regulation of Negr1 mrna expression, NEGR1 protein levels and neurite length whereas over expression enhanced Negr1 mrna expression, NEGR1 protein levels and increased neurite length. Meanwhile, another non-coding rna, microrna-203, was found to target the 3' untranslated region of the Negri mrna. Inhibition of microrna-203 led to increased expression of Negr1 mrna, elevated NEGR1 protein levels and increased neurite length. Conversely, microrna-203 over-expression decreased the level of Negr1 mrna, NEGR1 protein and neurite length. Neither microrna-203 nor the long non-coding rna, BC048612 could influence each other's expression. Hence, the long non-coding rna, BC048612, and microrna-203 were determined to be positive and negative regulators of Negr1 gene expression respectively. These processes have a direct effect on NEGR1 protein levels and neurite length, thus highlighting the importance of the regulatory non-coding rnas in modulating Negri gene expression for precise neuronal development. (C) 2015 Elsevier B.V. All rights reserved.

关键词： Cell adhesion molecules Negr1 non-coding rna Incrna mirna Neuronal maturation

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Large intergenic non-coding rna-RoR modulates reprogramming of human induced pluripotent stem cells

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NATURE GENETICS 2010年第12期42卷 1113-+页

作者： Loewer, Sabine Cabili, Moran N. Guttman, Mitchell Loh, Yuin-Han Thomas, Kelly Park, In Hyun Garber, Manuel Curran, Matthew Onder, Tamer Agarwal, Suneet Manos, Philip D. Datta, Sumon Lander, Eric S. Schlaeger, Thorsten M. Daley, George Q. Rinn, John L. Childrens Hosp Boston Manton Ctr Orphan Dis Res Div Pediat Hematol & Oncol Stem Cell Transplantat Program Boston MA USA Dana Farber Canc Inst Boston MA 02115 USA Harvard Univ Sch Med Dept Biol Chem & Mol Pharmacol Boston MA 02115 USA Harvard Stem Cell Inst Cambridge MA USA Childrens Hosp Boston Stem Cell Program Boston MA USA Harvard & Massachusetts Inst Technol Broad Inst Cambridge MA USA MIT Dept Biol Cambridge MA USA Harvard Univ Sch Med Dept Syst Biol Boston MA 02115 USA Brigham & Womens Hosp Div Hematol Boston MA 02115 USA Howard Hughes Med Inst Chevy Chase MD USA Harvard Univ Dept Stem Cell & Regenerat Biol Boston MA 02115 USA Harvard Univ Sch Med Dept Pathol Beth Israel Deaconess Med Ctr Boston MA 02115 USA

The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome(1-5), resulting in altered patterns of gene expression(2,6-9). Here we characterize the transcriptional reorganization of large intergenic non-coding rnas (lincrnas)(10,11) that occurs upon derivation of human iPSCs and identify numerous lincrnas whose expression is linked to pluripotency. Among these, we defined ten lincrnas whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincrnas are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincrna (lincrna-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincrnas in the derivation of pluripotent stem cells.

关键词： non-coding rna GENE expression EMBRYONIC stem cells TRANSCRIPTION factors CELL determination STEM cell research

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Linking deregulation of non-coding rna to the core pathophysiology of Alzheimer's disease: An integrative review

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PROGRESS IN NEUROBIOLOGY 2017年第0期156卷 1-68页

作者： Millan, Mark J. Inst Rech Servier Ctr Therapeut Innovat Neuropsychiat 125 Chemin Ronde F-78290 Croissy Sur Seine France

The human genome encodes a vast repertoire of protein non-coding rnas (ncrna), some specific to the brain. Micrornas, which interfere with the translation of target mrnas, are of particular interest since their deregulation has been implicated in neurodegenerative disorders like Alzheimer's disease (AD). However, it remains challenging to link the complex body of observations on mirnas and AD into a coherent framework. Using extensive graphical support, this article discusses how a diverse panoply of mirnas convergently and divergently impact (and are impacted by) core pathophysiological processes underlying AD: neuroinflammation and oxidative stress;aberrant generation of beta-amyloid-42 (A beta 42);anomalies in the production, cleavage and post-translational marking of Tau;impaired clearance of A beta 42 and Tau;perturbation of axonal organisation;disruption of synaptic plasticity;endoplasmic reticulum stress and the unfolded protein response;mitochondrial dysfunction;aberrant induction of cell cycle re-entry;and apoptotic loss of neurons. Intriguingly, some classes of mirna provoke these cellular anomalies, whereas others act in a counter-regulatory, protective mode. Moreover, changes in levels of certain species of mirna are a consequence of the above-mentioned anomalies. In addition to mirnas, circular rnas, pirnas, long non-coding rnas and other types of ncrna are being increasingly implicated in AD. Overall, a complex mesh of deregulated and multi-tasking ncrnas reciprocally interacts with core pathophysiological mechanisms underlying AD. Alterations in ncrnas can be detected in CSF and the circulation as well as the brain and are showing promise as biomarkers, with the ultimate goal clinical exploitation as targets for novel modes of symptomatic and course-altering therapy. (C) 2017 Elsevier Ltd. All rights reserved.

关键词： Microrna miR non-coding rna ncrna lncrna Long non-coding rna pirna Circular rna beta-amyloid Tau Endoplasmic reticulum Unfolded protein response Oxidative stress Secretase Cell cycle re-entry Apoptosis Autophagy Neuroinflammation Neurodegenerative Epigenetic

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A cautionary tale: the non-causal association between type 2 diabetes risk SNP, rs7756992, and levels of non-coding rna, CDKAL1-v1

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DIABETOLOGIA 2015年第4期58卷 745-748页

作者： Locke, Jonathan M. Wei, Fan-Yan Tomizawa, Kazuhito Weedon, Michael N. Harries, Lorna W. Univ Exeter Inst Biomed & Clin Sci Sch Med Exeter EX2 5DW Devon England Kumamoto Univ Dept Mol Physiol Fac Life Sci Kumamoto Japan

Intronic single nucleotide polymorphisms (SNPs) in the CDKAL1 gene are associated with risk of developing type 2 diabetes. A strong correlation between risk alleles and lower levels of the non-coding rna, CDKAL1-v1, has recently been reported in whole blood extracted from Japanese individuals. We sought to replicate this association in two independent cohorts: one using whole blood from white UK-resident individuals, and one using a collection of human pancreatic islets, a more relevant tissue type to study with respect to the aetiology of diabetes. Levels of CDKAL1-v1 were measured by real-time PCR using rna extracted from human whole blood (n = 70) and human pancreatic islets (n = 48). Expression with respect to genotype was then determined. In a simple linear regression model, expression of CDKAL1-v1 was associated with the lead type 2 diabetes-associated SNP, rs7756992, in whole blood and islets. However, these associations were abolished or substantially reduced in multiple regression models taking into account rs9366357 genotype: a moderately linked SNP explaining a much larger amount of the variation in CDKAL1-v1 levels, but not strongly associated with risk of type 2 diabetes. Contrary to previous findings, we provide evidence against a role for dysregulated expression of CDKAL1-v1 in mediating the association between intronic SNPs in CDKAL1 and susceptibility to type 2 diabetes. The results of this study illustrate how caution should be exercised when inferring causality from an association between disease-risk genotype and non-coding rna expression.

关键词： CDKAL1 Expression quantitative trait loci Genome-wide association studies non-coding rna Type 2 diabetes

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Identification of non-coding rna signatures in idiopathic pulmonary fibrosis

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IRISH JOUrnaL OF MEDICAL SCIENCE 2024年第4期193卷 1923-1927页

作者： Elek, Alperen Bozgeyik, Esra Caska, Halil Gocer, Zekihan Bozgeyik, Ibrahim Ege Univ Fac Med Izmir Turkiye Adiyaman Univ Vocat Sch Hlth Serv Dept Med Serv & Tech Adiyaman Turkiye Gaziantep Univ Fac Med Dept Med Biol Gaziantep Turkiye Gaziantep Univ Fac Med Gaziantep Turkiye Adiyaman Univ Fac Med Dept Med Biol TR-02040 Adiyaman Turkiye

Background Idiopathic pulmonary fibrosis (IPF) is a deadly, chronic, progressive, irreversible interstitial lung disease characterized by the formation of scar tissue resulting in permanent lung damage. The average survival time following diagnosis is only 3-5 years, with a 5-year survival rate shorter than that of many cancers. Alveolar epithelial cell injury followed by irregular repair is the primary pathological process observed in patients with IPF. An evident characteristic of IPF is the development of fibroblastic foci representing active fibrotic areas. Most of the cells within these foci are believed to be myofibroblasts, which are thought to be the primary source of abnormal extracellular matrix production in IPF. The lung phenotype in IPF is characterized by significantly different processes from healthy lungs, including irregular apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) pathways. Aims The exact cause of IPF is not fully understood and remains mysterious. It is not suppressing that non-coding rnas are involved in the development and progression of IPF. Accordingly, here we aimed to identify non-coding rna molecules during TGF beta-induced myofibroblast activation. Methods Differential expression and functional enrichment analysis were employed to reveal the impact of non-coding rnas during TGF beta-associated lung fibrosis. Results Remarkably, LOC101448202, CZ1P-ASNS, LINC01503, IER3-AS1, MIR503HG, CLMAT3, LINC02593, ACTA2-AS1, LOC102723692, LOC107985728, and LOC105371064 were identified to be differentially altered during TGF beta-stimulated myofibroblast activation. Conclusions These findings strongly suggest that the mechanism of lung fibrosis is heavily under control of non-coding rnas, and rna-based therapies could be a promising approach for future therapeutic interventions to lung fibrosis.

关键词： alpha-SMA ACTA2-AS1 Fibrosis non-coding rna Pulmonary Fibrosis

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A case for non-coding rna as a suitable biomarker of amyotrophic lateral sclerosis

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EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 2023年第12期23卷 1049-1051页

作者： Joilin, Greig Hafezparast, Majid Univ Sussex Sch Life Sci Brighton East Sussex England

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TUG1: a pivotal oncogenic long non-coding rna of human cancers

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CELL PROLIFERATION 2016年第4期49卷 471-475页

作者： Li, Zheng Shen, Jianxiong Chan, Matthew T. V. Wu, William Ka Kei Chinese Acad Med Sci Dept Orthoped Surg Peking Union Med Coll Hosp Beijing 100042 Peoples R China Peking Union Med Coll Beijing 100042 Peoples R China Chinese Univ Hong Kong Dept Anaesthesia & Intens Care Hong Kong Hong Kong Peoples R China Chinese Univ Hong Kong LKS Inst Hlth Sci State Key Lab Digest Dis Hong Kong Hong Kong Peoples R China

Long non-coding rnas (lncrnas) are a group greater than 200 nucleotides in length. An increasing number of studies has shown that lncrnas play important roles in diverse cellular processes, including proliferation, differentiation, apoptosis, invasion and chromatin remodelling. In this regard, deregulation of lncrnas has been documented in human cancers. TUG1 is a recently identified oncogenic lncrna whose aberrant upregulation has been detected in different types of cancer, including B-cell malignancies, oesophageal squamous cell carcinoma, bladder cancer, hepatocellular carcinoma and osteosarcoma. In these malignancies, knock-down of TUG1 has been shown to suppress cell proliferation, invasion and/or colony formation. Interestingly, TUG1 has been found to be downregulated in non-small cell lung carcinoma, indicative of its tissue-specific function in tumourigenesis. Pertinent to clinical practice, TUG1 may act as a prognostic biomarker for tumours. In this review, we summarize current knowledge concerning the role of TUG1 in tumour progression and discuss mechanisms associated with it.

关键词： non-coding rna NUCLEOTIDES CELL differentiation CELL proliferation APOPTOSIS CHROMATIN

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Transcriptional regulation of telomeric non-coding rna Implications on telomere biology, replicative senescence and cancer

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rna BIOLOGY 2010年第1期7卷 18-22页

作者： Caslini, Corrado Univ Michigan Sch Med Dept Pathol Ann Arbor MI 48109 USA

Telomeres, protective nucleoprotein structures located at the ends of eukaryotic chromosomes and until recently regarded as transcriptionally silent, are now known to be transcribed into non-coding rna molecules called TERRA. The function(s) of TERRA in telomere metabolism is now the subject of intense study given the implications these may have on fundamental biological processes such as aging and cancer. Here is an overview of what is currently known in the novel field of telomere transcription, with regard to the evidence on the possible role of TERRA in telomeric heterochromatin formation, in the epigenetic protection of telomeres from DNA repair mechanisms, and in the regulation of telomerase activity. The implications of TERRA transcriptional regulation on telomerase activity in cancer cells and on the perception of telomere length and control of replicative senescence in cells devoid of telomere maintenance mechanisms will be discussed.

关键词： telomere non-coding rna TERRA MLL replicative senescence DNA-damage response epigenetics

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