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

Marc R. Fabian | Zendy; Maja K. Cieplak-Rotowska | Zendy; Filipp Frank | Zendy; Masahiro Morita | Zendy; Jonathan Green | Zendy; Tharan Srikumar | Zendy; Bhushan Nagar | Zendy; Tadashi Yamamoto | Zendy; Brian Raught | Zendy; Thomas F. Duchaîne | Zendy; Nahum Sonenberg | Zendy

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

Author(s) -

Marc R. Fabian,

Maja K. Cieplak-Rotowska,

Filipp Frank,

Masahiro Morita,

Jonathan Green,

Tharan Srikumar,

Bhushan Nagar,

Tadashi Yamamoto,

Brian Raught,

Thomas F. Duchaîne,

Nahum Sonenberg

Publication year - 2011

Publication title -

nature structural and molecular biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.448

H-Index - 270

eISSN - 1545-9993

pISSN - 1545-9985

DOI - 10.1038/nsmb.2149

Subject(s) - argonaute , gene silencing , biology , psychological repression , genetics , microbiology and biotechnology , rasirna , rna interference , rna , gene , gene expression

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.

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