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A cyanobacterial non-coding rna, Yfr1, is required for growth under multiple stress conditions

PLANT AND CELL PHYSIOLOGY 2007年第9期48卷 1309-1318页

作者： Nakamura, Takahiro Naito, Kumiko Yokota, Naoto Sugita, Chieko Sugita, Mamoru Nagoya Univ Ctr Gene Res Nagoya Aichi 4648602 Japan

Small, regulatory, non-coding rna (ncrna) is involved in various cell functions in both prokaryotes and eukaryotes. However, information on ncrna in cyanobacteria is still scarce. We studied ncrna genes by computational screening to compare the intergenic regions of the Synechococcus elongatus PCC 6301 genome with the genomes of three freshwater cyanobacteria. We identified an ncrna gene in S. elongatus, which has been previously described as yfr1 in marine cyanobacteria. The S. elongatus yfr1 gene is 65 nucleotides long and is positioned between guaB and trxA. We found a high conservation of the yfr1 gene in most cyanobacterial lineages. A yfr1-deficient mutant showed reduced growth under various stress conditions, e.g. oxidative stress and high salt stress conditions, and showed unusual accumulation of sbtA mrna. A gel shift assay demonstrated interaction of the Yfr1 rna with sbtA mrna in vitro. This suggests that the sbtA transcript is a target rna for the Yfr1 rna.

关键词： cyanobacteria functional rna non-coding rna stress response Synechococcus elongatus

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Thioredoxin post-transcriptional regulation by H19 provides a new function to mrna-like non-coding rna

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ONCOGENE 2002年第10期21卷 1625-1631页

作者： Lottin, S Vercoutter-Edouart, AS Adriaenssens, E Czeszak, X Lemoine, J Roudbaraki, M Coll, J Hondermarck, H Dugimont, T Curgy, JJ USTL UPRES EA 1033 Dev Biol Lab F-59655 Villeneuve Dascq France Lab Immunopathol Cellulaire Malad Infect UMR 8527 F-59021 Lille France USTL CNRS UMR 8576 Chim Biol Lab F-59655 Villeneuve Dascq France USTL INSERM 9938 Lab Physiol & Physiopathol Prostate Humaine F-59655 Villeneuve Dascq France

Classically, the functional product of coding genes is a protein whose synthesis is directed by an mrna-template. However, in the last few years several genes yielding an mrna-like non-coding rna as a functional product have been identified. In most cases these transcripts are synthesized by the rna polymerase II, capped, spliced and polyadenylated, like classical mrna. These latter have non-conserved open reading frames and seem to be untranslated. Consequently, it has been proposed and admitted that these genes act at the rna level, and are so-called 'riboregulators'. H19 belongs to this class of gene and its role remains a matter of debate: for some authors it is an oncogene, for others a tumour suppressor. Here, we demonstrate, using a proteomic approach, that an H19 overexpression in human cancerous mammary epithelial cells stably transfected with genomic DNA containing the entire H19 gene is responsible for positively regulating at the post-transcriptional level the thioredoxin, a key protein of the cellular redox metabolism. Interestingly, this protein accumulates in many cancerous tissues, such as breast carcinomas in which we have also demonstrated an overexpression of the H19 gene.

关键词： H19 gene non-coding rna riboregulator proteomic thioredoxin oncogene

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SINEUP non-coding rna Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson's Disease

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MOLECULAR THERAPY 2020年第2期28卷 642-652页

作者： Espinoza, Stefano Scarpato, Margherita Damiani, Devid Manago, Francesca Mereu, Maddalena Contestabile, Andrea Peruzzo, Omar Carninci, Piero Santoro, Claudio Papaleo, Francesco Mingozzi, Federico Ronzitti, Giuseppe Zucchelli, Silvia Gustincich, Stefano Ist Italiano Tecnol Cent RNA Lab Via Morego 30 I-16263 Genoa Italy Ist Italiano Tecnol Dept Neurosci & Brain Technol Via Morego 30 I-16263 Genoa Italy Univ Padua Dipartimento Sci Farmaco Largo Meneghetti 2 I-35131 Padua Italy RIKEN Ctr Life Sci Technol Div Genom Technol Yokohama Kanagawa Japan Univ Piemonte Orientale Dept Hlth Sci I-28100 Novara Italy Univ Piemonte Orientale IRCAD I-28100 Novara Italy Univ Paris Saclay Univ Evry INSERM INTEGRAREGenethon F-91002 Evry France Scuola Int Avanzati SISSA Area Neurosci I-34012 Trieste Italy

Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson's disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression. Here we took advantage of SINEUPs, a new class of antisense long non-coding rna, that promote translation of partially overlapping sense protein-coding mrnas with no effects on their mrna levels. By synthesizing a SINEUP targeting Gdnf mrna, we were able to increase endogenous GDNF protein levels by about 2-fold. Adeno-associated virus (AAV) 9-mediated delivery in the striatum of wild-type (WT) mice led to an increase of endogenous GDNF protein for at least 6 months and the potentiation of the DA system's functions while showing no side effects. Furthermore, SINEUP-GDNF was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD neurochemical mouse model. Our data indicate that SINEUP-GDNF could represent a new strategy to increase endogenous GDNF protein levels in a more physiological manner for therapeutic treatments of PD.

关键词： SINEUP GDNF Parkinson’s disease non-coding rna gene therapy AAV

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The hallmarks of cancer A long non-coding rna point of view

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rna BIOLOGY 2012年第6期9卷 703-719页

作者： Gutschner, Tony Diederichs, Sven German Canc Res Ctr Helmholtz Univ Grp Mol RNA Biol & Canc Heidelberg Germany Heidelberg Univ Inst Pathol D-6900 Heidelberg Germany

With the advent of next generation sequencing methods and progress in transcriptome analysis, it became obvious that the human genome contains much more than just protein-coding genes. In fact, up to 70% of our genome is transcribed into rna that does not serve as templates for proteins. In this review, we focus on the emerging roles of these long non-coding rnas (lncrnas) in the field of tumor biology. Long ncrnas were found to be deregulated in several human cancers and show tissue-specific expression. Functional studies revealed a broad spectrum of mechanisms applied by lncrnas such as HOTAIR, MALAT1, ANRIL or lincrna-p21 to fulfill their functions. Here, we link the cellular processes influenced by long ncrnas to the hallmarks of cancer and therefore provide an ncrna point-of-view on tumor biology. This should stimulate new research directions and therapeutic options considering long ncrnas as novel prognostic markers and therapeutic targets.

关键词： non-coding rna ncrna lincrna gene expression carcinogenesis tumor biology cancer therapy MALAT1 HOTAIR XIST T-UCR

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Role of non-coding rna and heterochromatin in aneuploidy and cancer

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SEMINARS IN CANCER BIOLOGY 2008年第2期18卷 123-130页

作者： Pezer, Zeljka Ugarkovic, Durdica Rudjer Boskovic Inst Dept Mol Biol HR-10002 Zagreb Croatia

Abnormal chromosome content known as aneuploidy is the most common characteristic of human solid tumors. The molecular roots of aneuploidy lie in defective centromere/kinetochore assembly and function leading to improper chromosome segregation. These defects can be caused by mutations and/or by altered expression of diverse kinetochore proteins. In addition to proteins, non-coding rna deriving from centromeric repeats plays an active role, mostly through the rnai pathway, in the formation of pericentromeric and centromeric heterochromatin, both of them important for proper centromere function. We propose that stoichiometric expression of major kinetochore components such as non-coding centromeric rna and proteins is crucial for centromere/kinetochore assembly and function. Slight changes in expression of non-coding rna or mutations in the rna metabolic pathways induce chromosome instability, mis-segregation and aneuploidy, facilitating finally tumourigenesis. (C) 2008 Elsevier Ltd. All rights reserved.

关键词： aneuploidy cancer non-coding rna centromere heterochromatin

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Noisy silence non-coding rna and heterochromatin formation at repetitive elements

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EPIGENETICS 2014年第1期9卷 53-61页

作者： Bierhoff, Holger Postepska-Igielska, Anna Grummt, Ingrid DKFZ ZMBH Alliance German Canc Res Ctr Div Mol Biol Cell 2 Heidelberg Germany

A significant fraction of eukaryotic genomes comprises repetitive sequences, including rrna genes, centromeres, telomeres, and retrotransposons. Repetitive elements are hotspots for recombination and represent a serious challenge for genome integrity. Maintaining these repeated elements in a compact heterochromatic structure suppresses recombination and unwanted mutagenic transposition, and is therefore indispensable for genomic stability. Paradoxically, repetitive elements are not transcriptionally inert, but produce rna that has important functions in regulating and reinforcing the heterochromatic state. Here, we review the role of non-coding rna (ncrna) in recruiting chromatin-modifying enzymes to repetitive genomic loci to establish a repressive chromatin structure that safeguards chromosome integrity and genome stability.

关键词： non-coding rna heterochromatin repetitive elements rDNA centromeres telomeres retrotransposons

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non-coding transcription characterization and annotation A guide and web resource for non-coding rna databases

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rna BIOLOGY 2012年第3期9卷 274-282页

作者： Paschoal, Alexandre Rossi Maracaja-Coutinho, Vinicius Setubal, Joao Carlos Paulino Simoes, Zila Luz Verjovski-Almeida, Sergio Durham, Alan Mitchell Univ Sao Paulo Inst Matemat & Estat Dept Ciencia Comp Sao Paulo Brazil Univ Sao Paulo Inst Quim Dept Bioquim BR-01498 Sao Paulo Brazil Univ Tecnol Fed Parana Cornelio Procopio Brazil Univ Sao Paulo Fac Filosofia Ciencias & Letras Ribeirao Preto Dept Biol Sao Paulo Brazil Univ Sao Paulo Inst Matemat & Estat Programa Interunidades Bioinformat Sao Paulo Brazil

Large-scale transcriptome projects have shown that the number of rna transcripts not coding for proteins (non-coding rnas) is much larger than previously recognized. High-throughput technologies, coupled with bioinformatics approaches, have produced increasing amounts of data, highlighting the role of non-coding rnas (ncrnas) in biological processes. Data generated by these studies include diverse non-coding rna classes from organisms of different kingdoms, which were obtained using different experimental and computational assays. This has led to a rapid increase of specialized rna databases. The fast growth in the number of available databases makes integration of stored information a difficult task. We present here NRDR, a non-coding rna Databases Resource for information retrieval on ncrna databases (***). We performed a survey of 102 public databases on ncrnas and we have introduced four categorizations to classify these databases and to help researchers quickly search and find the information they need: rna family, information source, information content and available search mechanisms. NRDR is a useful databases searching tool that will facilitate research on ncrnas.

关键词： ncrna non-coding rna database transcription bioinformatics web tool

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SmProt: a database of small proteins encoded by annotated coding and non-coding rna loci

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BRIEFINGS IN BIOINFORMATICS 2018年第4期19卷 636-643页

作者： Hao, Yajing Zhang, Lili Niu, Yiwei Cai, Tanxi Luo, Jianjun He, Shunmin Zhang, Bao Zhang, Dejiu Qin, Yan Yang, Fuquan Chen, Runsheng Chinese Acad Sci Inst Biophys Key Lab RNA Biol Beijing 100101 Peoples R China Inst Biophys Key Lab RNA Biol Beijing Peoples R China Univ Chinese Acad Sci Beijing Peoples R China Chinese Acad Sci Inst Biophys Key Lab Prot & Peptide Pharmaceut Beijing Peoples R China Chinese Acad Sci Inst Biophys Lab Prote Beijing Peoples R China Chinese Acad Sci Inst Zool Key Lab Zool Systemat & Evolut Beijing Peoples R China

Small proteins is the general term for proteins with length shorter than 100 amino acids. Identification and functional studies of small proteins have advanced rapidly in recent years, and several studies have shown that small proteins play important roles in diverse functions including development, muscle contraction and DNA repair. Identification and characterization of previously unrecognized small proteins may contribute in important ways to cell biology and human health. Current databases are generally somewhat deficient in that they have either not collected small proteins systematically, or contain only predictions of small proteins in a limited number of tissues and species. Here, we present a specifically designed web-accessible database, small proteins database (SmProt, http://***/SmProt), which is a database documenting small proteins. The current release of SmProt incorporates 255 010 small proteins computationally or experimentally identified in 291 cell lines/tissues derived from eight popular species. The database provides a variety of data including basic information (sequence, location, gene name, organism, etc.) as well as specific information (experiment, function, disease type, etc.). To facilitate data extraction, SmProt supports multiple search options, including species, genome location, gene name and their aliases, cell lines/tissues, ORF type, gene type, PubMed ID and SmProt ID. SmProt also incorporates a service for the BLAST alignment search and provides a local UCSC Genome Browser. Additionally, SmProt defines a high-confidence set of small proteins and predicts the functions of the small proteins.

关键词： small proteins ribosome profiling non-coding rna sORFs

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Emerging fundamental roles for non-coding rna species in toxicology

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TOXICOLOGY 2008年第1期246卷 34-39页

作者： Taylor, Emma L. Gant, Timothy W. Univ Leicester Syst Toxicol Grp Med Res Council Toxicol Unit Leicester LE1 9HN Leics England

micrornas (mirnas) area large family of small regulatory rna molecules found in all multicellular organisms. Since their discovery in 2001, there has been impressive progress in mirna research, and a great deal is now known about the biosynthesis of mirnas and their regulatory role in translation. It is becoming increasingly clear that mirnas have fundamental roles to play in cellular responses to xenobiotic stress, the development of pathophysiological changes and other toxicological phenomenon such as susceptibility and resistance. Furthermore, the expression of mirnas. like many of the genes important in toxicology, can be regulated by xenobiotics and DNA methylation. In this article we review the present understanding of the mirna field with particular reference to toxicology. We also give an insight into our cur-rent projects within this exciting area and highlight some of the new challenges that now face mirna research. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

关键词： microrna toxicology mrna translation non-coding rna

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Restricted co-expression of Dlk1 and the reciprocally imprinted non-coding rna, Glk2:: Implications for cis-acting control

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DEVELOPMENTAL BIOLOGY 2007年第2期306卷 810-823页

作者： da Rocha, Simao T. Tevendale, Maxine Knowles, Edward Takada, Shuji Watkins, Marie Ferguson-Smith, Anne C. Univ Cambridge Dept Physiol Dev & Neurosci Cambridge CB2 3DY England

Dlk1 and Gtl2 are reciprocally imprinted neighboring genes located within a 1 Mb imprinted domain on murine distal chromosome 12. The two genes are expressed and developmentally regulated during mammalian embryogenesis. Dlk1/Pref1 encodes a transmembrane protein with homology to members of the Notch/Delta developmental signaling pathway and Gtl2 generates alternatively spliced poly-adenylated transcripts lacking a conserved open reading frame. An intergenic differentially methylated region (IG-DMR) located 13 kb upstream of Gtl2 has been shown to regulate imprinting throughout the domain by an as yet unknown mechanism. In order to gain insights into regulation at this domain and to compare it with imprinting control at other loci, we compared the expression profile of Dlk1 with Gtl2 during mouse embryogenesis in normal conceptuses and in those with uniparental disomy for chromosome 12. The expression profile of these genes suggests a causative role for Dlk1 and Gtl2 in the pathologies found in uniparental disomy animals, characterized by defects in skeletal muscle maturation, bone formation, placenta size and organization and prenatal lethality. Here, we show restricted overlap in cellular expression of these two genes throughout development. Dlk1 is imprinted and expressed in cell types within the lung, liver and placenta where Gtl2 is not expressed. Gtl2 is highly expressed in the central nervous system (CNS), whereas Dlk1 is found localized to specific regions such as the hypothalamus. Co-expression is observed in most of the mesodermal-derived tissues, notably the skeletal muscle where both genes are strongly co-expressed. In this tissue, Dlk1 shows a relaxation of imprinting with some expression from the maternal allele. These findings indicate that the general mechanism of imprinting at the stages analyzed is not through the co-ordinate non-coding rna or insulator mechanisms observed for other imprinted domains, and suggest that the two genes have independent

关键词： Dlk1 Gtl2 imprinting non-coding rna insulator uniparental disomy mouse development

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