Format

Send to

Choose Destination
Nat Struct Mol Biol. 2012 Feb 12;19(3):321-7. doi: 10.1038/nsmb.2230.

An alternative mode of microRNA target recognition.

Author information

1
Laboratory of Neuro-Oncology, The Rockefeller University, Howard Hughes Medical Institute, New York, New York, USA. swchi@skku.edu

Abstract

MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ~50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.

Comment in

PMID:
22343717
PMCID:
PMC3541676
DOI:
10.1038/nsmb.2230
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center