MiRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT

Marc R. Fabian, Maja K. Cieplak, Filipp Frank, Masahiro Morita, Jonathan Green, Tharan Srikumar, Bhushan Nagar, Tadashi Yamamoto, Brian Raught, Thomas F. Duchaine, Nahum Sonenberg

Research output: Contribution to journalArticlepeer-review

209 Scopus citations

Abstract

miRNAs recruit the miRNA-induced silencing complex (miRISC), which includes Argonaute and GW182 as core proteins. GW182 proteins effect translational repression and deadenylation of target mRNAs. However, the molecular mechanisms of GW182-mediated repression remain obscure. We show here that human GW182 independently interacts with the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Interaction of GW182 with CCR4-NOT is mediated by two newly discovered phylogenetically conserved motifs. Although either motif is sufficient to bind CCR4-NOT, only one of them can promote processive deadenylation of target mRNAs. Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT.

Original languageEnglish (US)
Pages (from-to)1211-1217
Number of pages7
JournalNature Structural and Molecular Biology
Volume18
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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