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 journalArticle

187 Citations (Scopus)

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 1 2011
Externally publishedYes

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MicroRNAs
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

MiRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. / Fabian, Marc R.; Cieplak, Maja K.; Frank, Filipp; Morita, Masahiro; Green, Jonathan; Srikumar, Tharan; Nagar, Bhushan; Yamamoto, Tadashi; Raught, Brian; Duchaine, Thomas F.; Sonenberg, Nahum.

In: Nature Structural and Molecular Biology, Vol. 18, No. 11, 01.11.2011, p. 1211-1217.

Research output: Contribution to journalArticle

Fabian, MR, Cieplak, MK, Frank, F, Morita, M, Green, J, Srikumar, T, Nagar, B, Yamamoto, T, Raught, B, Duchaine, TF & Sonenberg, N 2011, 'MiRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT', Nature Structural and Molecular Biology, vol. 18, no. 11, pp. 1211-1217. https://doi.org/10.1038/nsmb.2149
Fabian, Marc R. ; Cieplak, Maja K. ; Frank, Filipp ; Morita, Masahiro ; Green, Jonathan ; Srikumar, Tharan ; Nagar, Bhushan ; Yamamoto, Tadashi ; Raught, Brian ; Duchaine, Thomas F. ; Sonenberg, Nahum. / MiRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. In: Nature Structural and Molecular Biology. 2011 ; Vol. 18, No. 11. pp. 1211-1217.
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AU - Green, Jonathan

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