Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Struct Mol Biol. 2011 Sep 11;18(10):1139-46. doi: 10.1038/nsmb.2115.

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

Author information

  • 1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.

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.

PMID:
21909094
[PubMed - indexed for MEDLINE]
PMCID:
PMC3190056
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk