DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs

Recently, the attention of the research community has been focused on long non-coding RNAs (lncRNAs) and their physiological/pathological implications. As the number of experiments increase in a rapid rate and transcriptional units are better annotated, databases indexing lncRNA properties and function gradually become essential tools to this process. Aim of DIANA-LncBase (www.microrna.gr/LncBase) is to reinforce researchers’ attempts and unravel microRNA (miRNA)–lncRNA putative functional interactions. This study provides, for the first time, a comprehensive annotation of miRNA targets on lncRNAs. DIANA-LncBase hosts transcriptome-wide experimentally verified and computationally predicted miRNA recognition elements (MREs) on human and mouse lncRNAs. The analysis performed includes an integration of most of the available lncRNA resources, relevant high-throughput HITS-CLIP and PAR-CLIP experimental data as well as state-of-the-art in silico target predictions. The experimentally supported entries available in DIANA-LncBase correspond to >5000 interactions, while the computationally predicted interactions exceed 10 million. DIANA-LncBase hosts detailed information for each miRNA–lncRNA pair, such as external links, graphic plots of transcripts’ genomic location, representation of the binding sites, lncRNA tissue expression as well as MREs conservation and prediction scores.

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

[2]  C. Ponting,et al.  Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. , 2007, Genome research.

[3]  J. Mattick,et al.  Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation , 2010, BMC Neuroscience.

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

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

[6]  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.

[7]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[8]  Cole Trapnell,et al.  Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. , 2011, Genes & development.

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

[10]  B. Cullen,et al.  The imprinted H19 noncoding RNA is a primary microRNA precursor. , 2007, RNA.

[11]  R. Giegerich,et al.  Fast and effective prediction of microRNA/target duplexes. , 2004, RNA.

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

[13]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[14]  Scott B. Dewell,et al.  Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP , 2010, Cell.

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

[16]  Emily A. Vucic,et al.  Human Cancer Long Non-Coding RNA Transcriptomes , 2011, PloS one.

[17]  Jiayi Wang,et al.  CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer , 2010, Nucleic acids research.

[18]  Celso A. Espinoza,et al.  Characterization of the structure, function, and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription. , 2007, RNA.

[19]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

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

[21]  M. Kimmel,et al.  Conflict of interest statement. None declared. , 2010 .

[22]  Xiaohui Xie,et al.  Identifying novel constrained elements by exploiting biased substitution patterns , 2009, Bioinform..

[23]  Bronwen L. Aken,et al.  GENCODE: The reference human genome annotation for The ENCODE Project , 2012, Genome research.

[24]  J. Rinn,et al.  A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response , 2010, Cell.

[25]  A. Mele,et al.  Ago HITS-CLIP decodes miRNA-mRNA interaction maps , 2009, Nature.

[26]  V. Kim,et al.  Biogenesis of small RNAs in animals , 2009, Nature Reviews Molecular Cell Biology.

[27]  D. Cacchiarelli,et al.  A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA , 2011, Cell.

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

[29]  Carolyn J. Brown,et al.  The functional role of long non-coding RNA in human carcinomas , 2011, Molecular Cancer.

[30]  Andrea Califano,et al.  The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. , 2010, Cancer cell.

[31]  Ivo Grosse,et al.  Functional microRNA targets in protein coding sequences , 2012, Bioinform..

[32]  M. Kiebler,et al.  Faculty Opinions recommendation of Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. , 2009 .

[33]  Y. Hayashizaki,et al.  Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays. , 2003, Genome research.