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      TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support

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          Abstract

          As the relevant literature and the number of experiments increase at a super linear rate, databases that curate and collect experimentally verified microRNA (miRNA) targets have gradually emerged. These databases attempt to provide efficient access to this wealth of experimental data, which is scattered in thousands of manuscripts. Aim of TarBase 6.0 ( http://www.microrna.gr/tarbase) is to face this challenge by providing a significant increase of available miRNA targets derived from all contemporary experimental techniques (gene specific and high-throughput), while incorporating a powerful set of tools in a user-friendly interface. TarBase 6.0 hosts detailed information for each miRNA–gene interaction, ranging from miRNA- and gene-related facts to information specific to their interaction, the experimental validation methodologies and their outcomes. All database entries are enriched with function-related data, as well as general information derived from external databases such as UniProt, Ensembl and RefSeq. DIANA microT miRNA target prediction scores and the relevant prediction details are available for each interaction. TarBase 6.0 hosts the largest collection of manually curated experimentally validated miRNA–gene interactions (more than 65 000 targets), presenting a 16.5–175-fold increase over other available manually curated databases.

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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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            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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              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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                Author and article information

                Journal
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                January 2012
                January 2012
                30 November 2011
                30 November 2011
                : 40
                : D1 , Database issue
                : D222-D229
                Affiliations
                1IMIS Institute, ‘Athena’ Research Center, 11524 Athens, 2DIANA-Lab, Institute of Molecular Oncology, Biomedical Sciences Research Center ‘Alexander Fleming’, 16672 Vari, 3Laboratory for Experimental Surgery and Surgical Research ‘N.S. Christeas’, Medical School of Athens, University of Athens, 11527 Athens, Greece, 4Department of Pathology and Laboratory Medicine, Division of Neuropathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA and 5Department of Computer Science, School of Electrical and Computer Engineering, National Technical University of Athens, 15773 Zografou, Greece
                Author notes
                *To whom correspondence should be addressed. Tel: +30 210 9656310 (ext. 190); Fax: +30 210 9653934; Email: artemis@ 123456fleming.gr
                Correspondence may also be addressed to Ioannis S. Vlachos. Tel: +30 210 9656310 (ext. 190); Fax: +30 210 9653934; Email: vlachos@ 123456fleming.gr

                The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

                Article
                gkr1161
                10.1093/nar/gkr1161
                3245116
                22135297
                00eecee3-2907-4dee-a1ec-d488379bbaed
                © The Author(s) 2011. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 September 2011
                : 10 November 2011
                : 11 November 2011
                Page count
                Pages: 8
                Categories
                Articles

                Genetics
                Genetics

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