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dc.contributor.authorSchnall-Levin, Michael
dc.contributor.authorBerger, Bonnie
dc.contributor.authorZhao, Yong
dc.contributor.authorPerrimon, Norbert
dc.date.accessioned2013-08-14T12:43:07Z
dc.date.available2013-08-14T12:43:07Z
dc.date.issued2010-08
dc.date.submitted2010-05
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/79843
dc.description.abstractMicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate protein-coding genes posttranscriptionally. In animals, most known miRNA targeting occurs within the 3′UTR of mRNAs, but the extent of biologically relevant targeting in the ORF or 5′UTR of mRNAs remains unknown. Here, we develop an algorithm (MinoTar—miRNA ORF Targets) to identify conserved regulatory motifs within protein-coding regions and use it to estimate the number of preferentially conserved miRNA-target sites in ORFs. We show that, in Drosophila, preferentially conserved miRNA targeting in ORFs is as widespread as it is in 3′UTRs and that, while far less abundant, conserved targets in Drosophila 5′UTRs number in the hundreds. Using our algorithm, we predicted a set of high-confidence ORF targets and selected seven miRNA-target pairs from among these for experimental validation. We observed down-regulation by the miRNA in five out of seven cases, indicating our approach can recover functional sites with high confidence. Additionally, we observed additive targeting by multiple sites within a single ORF. Altogether, our results demonstrate that the scale of biologically important miRNA targeting in ORFs is extensive and that computational tools such as ours can aid in the identification of such targets. Further evidence suggests that our results extend to mammals, but that the extent of ORF and 5′UTR targeting relative to 3′UTR targeting may be greater in Drosophila.en_US
dc.description.sponsorshipAmerican Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshipen_US
dc.description.sponsorshipStarr Foundationen_US
dc.description.sponsorshipHertz Foundation (Fellowship)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1006172107en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleConserved microRNA targeting in Drosophila is as widespread in coding regions as in 3'UTRsen_US
dc.typeArticleen_US
dc.identifier.citationSchnall-Levin, M., Y. Zhao, N. Perrimon, and B. Berger. “Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3 UTRs.” Proceedings of the National Academy of Sciences 107, no. 36 (September 7, 2010): 15751-15756.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratoryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mathematicsen_US
dc.contributor.mitauthorSchnall-Levin, Michaelen_US
dc.contributor.mitauthorBerger, Bonnieen_US
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsSchnall-Levin, M.; Zhao, Y.; Perrimon, N.; Berger, B.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-2724-7228
mit.licensePUBLISHER_POLICYen_US


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