Weak Seed-pairing Stability and High Target-site Abundance Decrease the Proficiency of Lsy-6 and Other MicroRNAs

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2011 Sep 13

PMID 21909094

Citations 564

Authors

David M Garcia

Daehyun Baek

Chanseok Shin

George W Bell

Andrew Grimson

David P Bartel

Affiliations

Soon will be listed here.

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.

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