An alternative mode of microRNA target recognition

Sung Wook Chi, Gregory J. Hannon, Robert B. Darnell

Research output: Contribution to journalArticle

237 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)321-327
Number of pages7
JournalNature Structural and Molecular Biology
Volume19
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'An alternative mode of microRNA target recognition'. Together they form a unique fingerprint.

  • Cite this