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

  • Nat Struct Mol Biol. 2011 Oct 7;18(11):1211-7. doi: 10.1038/nsmb.2149.
Marc R Fabian  1 ,  Maja K Cieplak ,  Filipp Frank ,  Masahiro Morita ,  Jonathan Green ,  Tharan Srikumar ,  Bhushan Nagar ,  Tadashi Yamamoto ,  Brian Raught ,  Thomas F Duchaine ,  Nahum Sonenberg
Affiliations
  • 1. Department of Biochemistry, McGill University, Montreal, Canada.
PMID: 21984185 DOI: 10.1038/nsmb.2149
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.