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dc.contributor.authorZheng, Grace X. Y.
dc.contributor.authorRavi, Arvind
dc.contributor.authorGould, Genevieve Michelle
dc.contributor.authorBurge, Christopher B.
dc.contributor.authorSharp, Phillip A.
dc.date.accessioned2012-06-14T20:03:27Z
dc.date.available2012-06-14T20:03:27Z
dc.date.issued2011-09
dc.date.submitted2011-08
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/71158
dc.description.abstractVariations in microRNA (miRNA) gene and/or target repertoire are likely to be key drivers of phenotypic differences between species. To better understand these changes, we developed a computational method that identifies signatures of species-specific target site gain and loss associated with miRNA acquisition. Interestingly, several of the miRNAs implicated in mouse 3′ UTR evolution derive from a single rapidly expanded rodent-specific miRNA cluster. Located in the intron of Sfmbt2, a maternally imprinted polycomb gene, these miRNAs (referred to as the Sfmbt2 cluster) are expressed in both embryonic stem cells and the placenta. One abundant miRNA from the cluster, miR-467a, functionally overlaps with the mir-290-295 cluster in promoting growth and survival of mouse embryonic stem cells. Predicted novel targets of the remaining cluster members are enriched in pathways regulating cell survival. Two relevant species-specific target candidates, Lats2 and Dedd2, were validated in cultured cells. We suggest that the rapid evolution of the Sfmbt2 cluster may be a result of intersex conflict for growth regulation in early mammalian development and could provide a general model for the genomic response to acquisition of miRNAs and similar regulatory factors.en_US
dc.description.sponsorshipFannie and John Hertz Foundationen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01-GM34277)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant P01-CA42063)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Core Grant P30-CA14051)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1112772108en_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.titleGenome-wide impact of a recently expanded microRNA cluster in mouseen_US
dc.typeArticleen_US
dc.identifier.citationZheng, G. X. Y. et al. “Genome-wide Impact of a Recently Expanded microRNA Cluster in Mouse.” Proceedings of the National Academy of Sciences 108.38 (2011): 15804–15809. Web. ©2011 by the National Academy of Sciences.en_US
dc.contributor.departmentWhitaker College of Health Sciences and Technologyen_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.approverBurge, Christopher B.
dc.contributor.mitauthorZheng, Grace X. Y.
dc.contributor.mitauthorRavi, Arvind
dc.contributor.mitauthorGould, Genevieve Michelle
dc.contributor.mitauthorBurge, Christopher B.
dc.contributor.mitauthorSharp, Phillip A.
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.orderedauthorsZheng, G. X. Y.; Ravi, A.; Gould, G. M.; Burge, C. B.; Sharp, P. A.en
dc.identifier.orcidhttps://orcid.org/0000-0001-6980-817X
dc.identifier.orcidhttps://orcid.org/0000-0003-1465-1691
dspace.mitauthor.errortrue
mit.licensePUBLISHER_POLICYen_US


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