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      DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions

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          Abstract

          microRNAs (miRNAs) are short non-coding RNA species, which act as potent gene expression regulators. Accurate identification of miRNA targets is crucial to understanding their function. Currently, hundreds of thousands of miRNA:gene interactions have been experimentally identified. However, this wealth of information is fragmented and hidden in thousands of manuscripts and raw next-generation sequencing data sets. DIANA-TarBase was initially released in 2006 and it was the first database aiming to catalog published experimentally validated miRNA:gene interactions. DIANA-TarBase v7.0 ( http://www.microrna.gr/tarbase) aims to provide for the first time hundreds of thousands of high-quality manually curated experimentally validated miRNA:gene interactions, enhanced with detailed meta-data. DIANA-TarBase v7.0 enables users to easily identify positive or negative experimental results, the utilized experimental methodology, experimental conditions including cell/tissue type and treatment. The new interface provides also advanced information ranging from the binding site location, as identified experimentally as well as in silico, to the primer sequences used for cloning experiments. More than half a million miRNA:gene interactions have been curated from published experiments on 356 different cell types from 24 species, corresponding to 9- to 250-fold more entries than any other relevant database. DIANA-TarBase v7.0 is freely available.

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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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            miRecords: an integrated resource for microRNA–target interactions

            MicroRNAs (miRNAs) are an important class of small noncoding RNAs capable of regulating other genes’ expression. Much progress has been made in computational target prediction of miRNAs in recent years. More than 10 miRNA target prediction programs have been established, yet, the prediction of animal miRNA targets remains a challenging task. We have developed miRecords, an integrated resource for animal miRNA–target interactions. The Validated Targets component of this resource hosts a large, high-quality manually curated database of experimentally validated miRNA–target interactions with systematic documentation of experimental support for each interaction. The current release of this database includes 1135 records of validated miRNA–target interactions between 301 miRNAs and 902 target genes in seven animal species. The Predicted Targets component of miRecords stores predicted miRNA targets produced by 11 established miRNA target prediction programs. miRecords is expected to serve as a useful resource not only for experimental miRNA researchers, but also for informatics scientists developing the next-generation miRNA target prediction programs. The miRecords is available at http://miRecords.umn.edu/miRecords.
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              Ago HITS-CLIP decodes miRNA-mRNA interaction maps

              Summary MicroRNAs (miRNAs) play critical roles in the regulation of gene expression. However, since miRNA activity requires base pairing with only 6-8 nucleotides of mRNA, predicting target mRNAs is a major challenge. Recently, high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) has identified functional protein-RNA interaction sites. Here we use HITS-CLIP to covalently crosslink native Argonaute (Ago) protein-RNA complexes in mouse brain. This produced two simultaneous datasets—Ago-miRNA and Ago-mRNA binding sites—that were combined with bioinformatic analysis to identify miRNA-target mRNA interaction sites. We validated genome-wide interaction maps for miR-124, and generated additional maps for the 20 most abundant miRNAs present in P13 mouse brain. Ago HITS-CLIP provides a general platform for exploring the specificity and range of miRNA action in vivo, and identifies precise sequences for targeting clinically relevant miRNA-mRNA interactions.
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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
                28 January 2015
                21 November 2014
                21 November 2014
                : 43
                : Database issue , Database issue
                : D153-D159
                Affiliations
                [1 ]DIANA-Lab, Department of Electrical & Computer Engineering, University of Thessaly, 382 21 Volos, Greece
                [2 ]Laboratory for Experimental Surgery and Surgical Research ‘N.S. Christeas’, Medical School of Athens, University of Athens, 11527 Athens, Greece
                [3 ]‘Athena’ Research and Innovation Center, 11524 Athens, Greece
                [4 ]School of Electrical and Computer Engineering, NTUA, 15773 Zografou, Greece
                [5 ]Department of Informatics and Telecommunications, Postgraduate Program: ‘Information Technologies in Medicine and Biology’, University of Athens, 15784 Athens, Greece
                [6 ]Department of Electrical & Computer Engineering, University of Thessaly, 382 21 Volos, Greece
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +30 24210 74758; Fax: +30 24210 74997; Email: arhatzig@ 123456uth.gr Correspondence may also be addressed to Tel: +30 210 6875415; Fax: +30 6856804; Email: dalamag@ 123456imis.athena-innovation.gr Correspondence may also be addressed to Tel: +30 24210 74758; Fax: +30 24210 74997; Email: ivlachos@ 123456lessr.eu
                Article
                10.1093/nar/gku1215
                4383989
                25416803
                de237fd4-b18b-4eda-945d-be47d651999b
                © The Author(s) 2014. 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
                : 06 November 2014
                : 05 November 2014
                : 06 October 2014
                Page count
                Pages: 7
                Categories
                Database Issue
                Custom metadata
                28 January 2015

                Genetics
                Genetics

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