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dc.contributor.author남진우-
dc.date.accessioned2017-04-25T01:13:08Z-
dc.date.available2017-04-25T01:13:08Z-
dc.date.issued2015-08-
dc.identifier.citationELIFE, v. 4, NO e05005, Page. 1-38en_US
dc.identifier.issn2050-084X-
dc.identifier.urihttps://elifesciences.org/content/4/e05005-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/26925-
dc.description.abstractMicroRNA targets are often recognized through pairing between the miRNA seed region and complementary sites within target mRNAs, but not all of these canonical sites are equally effective, and both computational and in vivo UV-crosslinking approaches suggest that many mRNAs are targeted through non-canonical interactions. Here, we show that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical. Accordingly, we developed an improved quantitative model of canonical targeting, using a compendium of experimental datasets that we pre-processed to minimize confounding biases. This model, which considers site type and another 14 features to predict the most effectively targeted mRNAs, performed significantly better than existing models and was as informative as the best high-throughput in vivo crosslinking approaches. It drives the latest version of TargetScan (v7.0; targetscan.org), thereby providing a valuable resource for placing miRNAs into gene-regulatory networks.en_US
dc.description.sponsorshipWe thank the Bioinformatics and Research Computing group at the Whitehead Institute (I Barrasa, B Yuan, Y Huang, and P Thiru) for help implementing improvements to the TargetScan website, A Subtelny for providing insight into positional effects of the miRNA seed, I Ulitsky for initial help with 3P-seq analysis, R Friedman for discussions regarding the computation of P<INF>CT</INF> parameters, T Tuschl for sharing an unpublished list of the most frequently sequenced human miRNA isoforms, G Agarwal for discussions regarding normalization techniques, G Kudla for help processing the microarray data from the CLASH study, SW Chi and RB Darnell for confirmation of the mRNAs identified as miR-124 targets in their dCLIP study, O Rissland and J Guo for critical reading of the manuscript, and members of the Bartel lab for helpful discussions. This work was supported by a National Science Foundation Graduate Research Fellowship (to VA) and an NIH grant GM067031 (to DPB). DPB is an investigator of the Howard Hughes Medical Institute.en_US
dc.language.isoenen_US
dc.publisherELIFE SCIENCES PUBLICATIONS LTDen_US
dc.subjectGENOME BROWSER DATABASEen_US
dc.subjectBINDING-SITESen_US
dc.subjectALTERNATIVE POLYADENYLATIONen_US
dc.subjectTRANSLATIONAL REPRESSIONen_US
dc.subjectWIDE IDENTIFICATIONen_US
dc.subjectANIMAL DEVELOPMENTen_US
dc.subjectPROTEIN-SYNTHESISen_US
dc.subjectGENE-EXPRESSIONen_US
dc.subjectOFF-TARGETSen_US
dc.subjectPAR-CLIPen_US
dc.titlePredicting effective microRNA target sites in mammalian mRNAsen_US
dc.typeArticleen_US
dc.relation.noe05005-
dc.relation.volume4-
dc.identifier.doi10.7554/eLife.05005-
dc.relation.page1-38-
dc.relation.journalELIFE-
dc.contributor.googleauthorAgarwal, Vikram-
dc.contributor.googleauthorBell, George W.-
dc.contributor.googleauthorNam, Jin Wu-
dc.contributor.googleauthorBartel, David P.-
dc.relation.code2015012574-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF NATURAL SCIENCES[S]-
dc.sector.departmentDEPARTMENT OF LIFE SCIENCE-
dc.identifier.pidjwnam-


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