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      miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

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          Abstract

          MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database ( http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system.

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          Prediction of mammalian microRNA targets.

          MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
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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
                January 2014
                4 December 2013
                4 December 2013
                : 42
                : D1 , Database issue
                : D78-D85
                Affiliations
                1Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 300, Taiwan, 2Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 402, Taiwan, 3Department of Computer Science and Engineering, National Chung Hsing University, Taichung 402, Taiwan, 4Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan, 5Molecular Bioinformatics Center, National Chiao Tung University, Hsinchu 300, Taiwan, 6Graduate Department of Clinical Pharmacy, Taipei Medical University, Taipei 110, Taiwan, 7Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 300, Taiwan, 8Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei 110, Taiwan, 9Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu 300, Taiwan, 10Mackay Medicine, Nursing and Management College, Taipei 112, Taiwan, 11Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan, and 12Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                Author notes
                *To whom correspondence should be addressed. Tel: +886 3 5712121 (ext. 56952); Fax: +886 3 5729288; Email: bryan@ 123456mail.nctu.edu.tw
                Correspondence may also be addressed to Chun-Chi Liu. Tel: +886 4 22840338 (ext. 7031); Fax: +886 4 22859329; Email: jimliu@ 123456nchu.edu.tw

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

                Article
                gkt1266
                10.1093/nar/gkt1266
                3965058
                24304892
                f69fabaa-f68d-484d-a2b3-01b394c06d78
                © The Author(s) 2013. 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 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@oup.com

                History
                : 14 September 2013
                : 5 November 2013
                : 12 November 2013
                Page count
                Pages: 8
                Categories
                I. Nucleic acid sequence, structure and regulation
                Custom metadata
                1 January 2014

                Genetics
                Genetics

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