dc.contributor.author | Garcia, David M. | |
dc.contributor.author | Baek, Daehyun | |
dc.contributor.author | Shin, Chanseok | |
dc.contributor.author | Bell, George W. | |
dc.contributor.author | Grimson, Andrew | |
dc.contributor.author | Bartel, David | |
dc.date.accessioned | 2013-12-19T17:04:25Z | |
dc.date.available | 2013-12-19T17:04:25Z | |
dc.date.issued | 2011-09 | |
dc.date.submitted | 2010-12 | |
dc.identifier.issn | 1545-9993 | |
dc.identifier.issn | 1545-9985 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/82943 | |
dc.description.abstract | Most 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.sponsorship | National Institutes of Health (U.S.) (grant GM067031) | en_US |
dc.description.sponsorship | Seoul National University (Research Settlement Fund) | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute (Investigator) | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/nsmb.2115 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike 3.0 | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Garcia, 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.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Garcia, David M. | en_US |
dc.contributor.mitauthor | Baek, Daehyun | en_US |
dc.contributor.mitauthor | Shin, Chanseok | en_US |
dc.contributor.mitauthor | Bell, George W. | en_US |
dc.contributor.mitauthor | Grimson, Andrew | en_US |
dc.contributor.mitauthor | Bartel, David | en_US |
dc.relation.journal | Nature Structural & Molecular Biology | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Garcia, David M; Baek, Daehyun; Shin, Chanseok; Bell, George W; Grimson, Andrew; Bartel, David P | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3872-2856 | |
mit.license | OPEN_ACCESS_POLICY | en_US |
mit.metadata.status | Complete | |