lncRNAMap: A map of putative regulatory functions in the long non-coding transcriptome

BACKGROUND Recent studies have demonstrated the importance of long non-coding RNAs (lncRNAs) in chromatin remodeling, and in transcriptional and post-transcriptional regulation. However, only a few specific lncRNAs are well understood, whereas others are completely uncharacterized. To address this, there is a need for user-friendly platform to studying the putative regulatory functions of human lncRNAs. DESCRIPTION lncRNAMap is an integrated and comprehensive database relating to exploration of the putative regulatory functions of human lncRNAs with two mechanisms of regulation, by encoding siRNAs and by acting as miRNA decoys. To investigate lncRNAs producing siRNAs that regulate protein-coding genes, lncRNAMap integrated small RNAs (sRNAs) that were supported by publicly available deep sequencing data from various sRNA libraries and constructed lncRNA-derived siRNA-target interactions. In addition, lncRNAMap demonstrated that lncRNAs can act as targets for miRNAs that would otherwise regulate protein-coding genes. Previously studies indicated that intergenic lncRNAs (lincRNAs) either positive or negative regulated neighboring genes, therefore, lncRNAMap surveyed neighboring genes within a 1Mb distance from the genomic location of specific lncRNAs and provided the expression profiles of lncRNA and its neighboring genes. The gene expression profiles may supply the relationship between lncRNA and its neighboring genes. CONCLUSIONS lncRNAMap is a powerful user-friendly platform for the investigation of putative regulatory functions of human lncRNAs with producing siRNAs and acting as miRNA decoy. lncRNAMap is freely available on the web at http://lncRNAMap.mbc.nctu.edu.tw/.

[1]  P. Hevezi,et al.  Gene expression analyses reveal molecular relationships among 20 regions of the human CNS , 2006, Neurogenetics.

[2]  G. Kreiman,et al.  Widespread transcription at neuronal activity-regulated enhancers , 2010, Nature.

[3]  T. Derrien,et al.  Long Noncoding RNAs with Enhancer-like Function in Human Cells , 2010, Cell.

[4]  Jan Krüger,et al.  RNAhybrid: microRNA target prediction easy, fast and flexible , 2006, Nucleic Acids Res..

[5]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[6]  Tsippi Iny Stein,et al.  In-silico human genomics with GeneCards , 2011, Human Genomics.

[7]  Leonie Ringrose,et al.  Non-coding RNAs in Polycomb/Trithorax regulation , 2009, RNA biology.

[8]  Jayoung Choi,et al.  A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. , 2007, Genes & development.

[9]  Ryan D. Morin,et al.  Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. , 2008, Genome research.

[10]  Lennart Martens,et al.  LNCipedia: a database for annotated human lncRNA transcript sequences and structures , 2012, Nucleic Acids Res..

[11]  Tim R. Mercer,et al.  NRED: a database of long noncoding RNA expression , 2008, Nucleic Acids Res..

[12]  T. Gingeras,et al.  Genome-wide transcription and the implications for genomic organization , 2007, Nature Reviews Genetics.

[13]  Alexander Deiters,et al.  Small Molecule Modifiers of the microRNA and RNA Interference Pathway , 2010, The AAPS Journal.

[14]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[15]  Paulo P. Amaral,et al.  RNA regulation of epigenetic processes , 2009, BioEssays : news and reviews in molecular, cellular and developmental biology.

[16]  Gautier Koscielny,et al.  Ensembl 2012 , 2011, Nucleic Acids Res..

[17]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[18]  John S. Mattick,et al.  lncRNAdb: a reference database for long noncoding RNAs , 2010, Nucleic Acids Res..

[19]  Howard Y. Chang,et al.  Long noncoding RNA in genome regulation , 2010, RNA biology.

[20]  Ana Kozomara,et al.  miRBase: integrating microRNA annotation and deep-sequencing data , 2010, Nucleic Acids Res..

[21]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[22]  Li Lin,et al.  Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. , 2011, Cancer cell.

[23]  Hongmin Li,et al.  A Precisely Regulated Gene Expression Cassette Potently Modulates Metastasis and Survival in Multiple Solid Cancers , 2008, PLoS genetics.

[24]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[25]  Gene W. Yeo,et al.  Divergent Transcription from Active Promoters , 2008, Science.

[26]  John J Rossi,et al.  Biogenesis and function of endogenous and exogenous siRNAs , 2010, Wiley interdisciplinary reviews. RNA.

[27]  Kiyoshi Asai,et al.  The Functional RNA Database 3.0: databases to support mining and annotation of functional RNAs , 2008, Nucleic Acids Res..

[28]  K. Struhl.  Transcriptional noise and the fidelity of initiation by RNA polymerase II , 2007, Nature Structural &Molecular Biology.

[29]  Xing Chen,et al.  LncRNADisease: a database for long-non-coding RNA-associated diseases , 2012, Nucleic Acids Res..

[30]  Hui Xiao,et al.  NONCODE v3.0: integrative annotation of long noncoding RNAs , 2011, Nucleic Acids Res..

[31]  Sibum Sung,et al.  Long noncoding RNA: unveiling hidden layer of gene regulatory networks. , 2012, Trends in plant science.

[32]  C. Ponting,et al.  Catalogues of mammalian long noncoding RNAs: modest conservation and incompleteness , 2009, Genome Biology.

[33]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[34]  Jennifer A. Mitchell,et al.  The Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin , 2008, Science.

[35]  Robert Blelloch,et al.  Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. , 2008, Genes & development.

[36]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

[37]  Hsien-Da Huang,et al.  pseudoMap: an innovative and comprehensive resource for identification of siRNA-mediated mechanisms in human transcribed pseudogenes , 2013, Database J. Biol. Databases Curation.

[38]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[39]  Dominic P. Norris,et al.  The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus , 1992, Cell.

[40]  Anton J. Enright,et al.  Human MicroRNA Targets , 2004, PLoS biology.

[41]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[42]  J. Rinn,et al.  lincRNAs act in the circuitry controlling pluripotency and differentiation , 2011, Nature.

[43]  Ron Edgar,et al.  Gene Expression Omnibus ( GEO ) : Microarray data storage , submission , retrieval , and analysis , 2008 .

[44]  Howard Y. Chang,et al.  Genome regulation by long noncoding RNAs. , 2012, Annual review of biochemistry.

[45]  Beth Israel,et al.  Decision letter: Replication Study: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology , 2010 .

[46]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[47]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[48]  M. Gerstein,et al.  Annotating non-coding regions of the genome , 2010, Nature Reviews Genetics.

[49]  Fred H. Gage,et al.  Alternative Splicing Events Identified in Human Embryonic Stem Cells and Neural Progenitors , 2007, PLoS Comput. Biol..

[50]  Jeannie T. Lee.  Epigenetic Regulation by Long Noncoding RNAs , 2012, Science.

[51]  Maciej Szymanski,et al.  Noncoding RNAs database (ncRNAdb) , 2007, Nucleic Acids Res..

[52]  Hsien-Da Huang,et al.  Transcribed pseudogene ψPPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma , 2013, Nucleic acids research.

[53]  Debora S. Marks,et al.  miRcode: a map of putative microRNA target sites in the long non-coding transcriptome , 2012, Bioinform..

[54]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[55]  Howard Y. Chang,et al.  Molecular mechanisms of long noncoding RNAs. , 2011, Molecular cell.

[56]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Martin Reczko,et al.  DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs , 2012, Nucleic Acids Res..