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dc.contributor.authorGarcia, David M.
dc.contributor.authorBaek, Daehyun
dc.contributor.authorShin, Chanseok
dc.contributor.authorBell, George W.
dc.contributor.authorGrimson, Andrew
dc.contributor.authorBartel, David
dc.date.accessioned2013-12-19T17:04:25Z
dc.date.available2013-12-19T17:04:25Z
dc.date.issued2011-09
dc.date.submitted2010-12
dc.identifier.issn1545-9993
dc.identifier.issn1545-9985
dc.identifier.urihttp://hdl.handle.net/1721.1/82943
dc.description.abstractMost metazoan microRNAs (miRNAs) target many genes for repression, but the nematode lsy-6 miRNA is much less proficient. Here we show that the low proficiency of lsy-6 can be recapitulated in HeLa cells and that miR-23, a mammalian miRNA, also has low proficiency in these cells. Reporter results and array data indicate two properties of these miRNAs that impart low proficiency: their weak predicted seed-pairing stability (SPS) and their high target-site abundance (TA). These two properties also explain differential propensities of small interfering RNAs (siRNAs) to repress unintended targets. Using these insights, we expand the TargetScan tool for quantitatively predicting miRNA regulation (and siRNA off-targeting) to model differential miRNA (and siRNA) proficiencies, thereby improving prediction performance. We propose that siRNAs designed to have both weaker SPS and higher TA will have fewer off-targets without compromised on-target activity.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant GM067031)en_US
dc.description.sponsorshipSeoul National University (Research Settlement Fund)en_US
dc.description.sponsorshipHoward Hughes Medical Institute (Investigator)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nsmb.2115en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourcePMCen_US
dc.titleWeak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAsen_US
dc.typeArticleen_US
dc.identifier.citationGarcia, David M, Daehyun Baek, Chanseok Shin, George W Bell, Andrew Grimson, and David P Bartel. “Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs.” Nature Structural & Molecular Biology 18, no. 10 (September 11, 2011): 1139-1146.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorGarcia, David M.en_US
dc.contributor.mitauthorBaek, Daehyunen_US
dc.contributor.mitauthorShin, Chanseoken_US
dc.contributor.mitauthorBell, George W.en_US
dc.contributor.mitauthorGrimson, Andrewen_US
dc.contributor.mitauthorBartel, Daviden_US
dc.relation.journalNature Structural & Molecular Biologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsGarcia, David M; Baek, Daehyun; Shin, Chanseok; Bell, George W; Grimson, Andrew; Bartel, David Pen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-3872-2856
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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