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      DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts

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          Abstract

          microRNAs (miRNAs) are short non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of coding gene expression. Long non-coding RNAs (lncRNAs) have been recently reported to interact with miRNAs. The sponge-like function of lncRNAs introduces an extra layer of complexity in the miRNA interactome. DIANA-LncBase v1 provided a database of experimentally supported and in silico predicted miRNA Recognition Elements (MREs) on lncRNAs. The second version of LncBase ( www.microrna.gr/LncBase) presents an extensive collection of miRNA:lncRNA interactions. The significantly enhanced database includes more than 70 000 low and high-throughput, (in)direct miRNA:lncRNA experimentally supported interactions, derived from manually curated publications and the analysis of 153 AGO CLIP-Seq libraries. The new experimental module presents a 14-fold increase compared to the previous release. LncBase v2 hosts in silico predicted miRNA targets on lncRNAs, identified with the DIANA-microT algorithm. The relevant module provides millions of predicted miRNA binding sites, accompanied with detailed metadata and MRE conservation metrics. LncBase v2 caters information regarding cell type specific miRNA:lncRNA regulation and enables users to easily identify interactions in 66 different cell types, spanning 36 tissues for human and mouse. Database entries are also supported by accurate lncRNA expression information, derived from the analysis of more than 6 billion RNA-Seq reads.

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          Most cited references17

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

            The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
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              Gene silencing by microRNAs: contributions of translational repression and mRNA decay.

              Despite their widespread roles as regulators of gene expression, important questions remain about target regulation by microRNAs. Animal microRNAs were originally thought to repress target translation, with little or no influence on mRNA abundance, whereas the reverse was thought to be true in plants. Now, however, it is clear that microRNAs can induce mRNA degradation in animals and, conversely, translational repression in plants. Recent studies have made important advances in elucidating the relative contributions of these two different modes of target regulation by microRNAs. They have also shed light on the specific mechanisms of target silencing, which, although it differs fundamentally between plants and animals, shares some common features between the two kingdoms.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                04 January 2016
                26 November 2015
                26 November 2015
                : 44
                : Database issue , Database issue
                : D231-D238
                Affiliations
                [1 ]DIANA-Lab, Department of Computer & Communication Engineering, University of Thessaly, 382 21, Volos, Greece
                [2 ]Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, 11521, Athens, Greece
                [3 ]Laboratory for Experimental Surgery and Surgical Research ‘N.S. Christeas’, Medical School of Athens, University of Athens, 11527, Greece
                [4 ]‘Athena’ Research and Innovation Center, 11524, Athens, Greece
                [5 ]School of Electrical and Computer Engineering, NTUA, 15773 Zografou, Greece
                [6 ]University of Peloponnisos, Department of Informatics and Telecommunications, 22100, Tripoli, Greece
                [7 ]Greek Research and Technology Network (GRNET), Athens 11527, Greece
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +30 24210 74758; Fax: +30 24210 74997; Email: arhatzig@ 123456inf.uth.gr
                Correspondence may also be addressed to Theodore Dalamagas. Tel: +30 210 6875415; Fax: +30 6856804; Email: dalamag@ 123456imis.athena-innovation.gr
                Correspondence may also be addressed to Maria D. Paraskevopoulou. Tel: +30 24210 74758; Fax: +30 24210 74997; Email: mparaskevopoulou@ 123456inf.uth.gr
                []Equal Contribution.
                Article
                10.1093/nar/gkv1270
                4702897
                26612864
                10d44bb0-8473-4a9f-a5d3-1fbce9cf333d
                © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 3 November 2015
                : 2 November 2015
                : 30 September 2015
                Page count
                Pages: 8
                Categories
                Database Issue
                Custom metadata
                04 January 2016

                Genetics
                Genetics

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