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
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
收藏
页码:1211 / U52
页数:8
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