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

被引：247

作者：

Fabian, Marc R. ^{[1
,2
]}

Cieplak, Maja K. ^{[3
]}

Frank, Filipp ^{[1
,2
]}

Morita, Masahiro ^{[1
,2
,4
]}

Green, Jonathan ^{[1
,2
]}

Srikumar, Tharan ^{[5
]}

Nagar, Bhushan ^{[1
,2
]}

Yamamoto, Tadashi ^{[4
]}

Raught, Brian ^{[5
]}

Duchaine, Thomas F. ^{[1
,2
]}

Sonenberg, Nahum ^{[1
,2
]}

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ, Canada

[2] McGill Univ, Goodman Canc Ctr, Montreal, PQ, Canada

[3] Warsaw Univ, Dept Biophys, Inst Expt Phys, Warsaw, Poland

[4] Univ Tokyo, Inst Med Sci, Dept Canc Biol, Tokyo, Japan

[5] Univ Toronto, Ontario Canc Inst, Toronto, ON, Canada

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 11期

基金：

加拿大健康研究院;

关键词：

MESSENGER-RNA DECAY; C-TERMINAL DOMAIN; TRANSLATIONAL REPRESSION; POLY(A)-BINDING PROTEIN; POLY(A) NUCLEASE; SACCHAROMYCES-CEREVISIAE; COMPLEX; ARGONAUTE; BINDING; IDENTIFICATION;

D O I：

10.1038/nsmb.2149

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1211 / U52

页数：8

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