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PMID: 21909094 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs.

Nature structural & molecular biology ·Vol. 18 ·No. 10 ·2011-09-11 ·Pages 1139-46

Garcia DM, Baek D, Shin C, Bell GW, Grimson A, Bartel DP

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.

MeSH Terms
3' Untranslated Regions Animals Caenorhabditis elegans/genetics HeLa Cells Humans MicroRNAs/genetics,metabolism
Chemicals
3' Untranslated Regions MicroRNAs
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Garcia David M
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Baek Daehyun
Shin Chanseok
Bell George W
Grimson Andrew
Bartel David P
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2115
Published
2011-09-11
Epub
2011-00-11
Pages
1139-46
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3190056
Subset
IM
Grants
NIGMS NIH HHS · R01 GM067031-08 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM067031-06 · United States
NIGMS NIH HHS · R01 GM067031 · United States
NIGMS NIH HHS · GM067031 · United States
NIGMS NIH HHS · R01 GM067031-07 · United States
External Links
PubMed source DOI: 10.1038/nsmb.2115 PMC Full Text View journal details
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