miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT
miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT
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DOI：
10.1038/nsmb.2149
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发表时间：
2011-11-01
影响因子：
16.8
通讯作者：
Sonenberg, Nahum
中科院分区：
文献类型：
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作者：
Fabian, Marc R.;Cieplak, Maja K.;Sonenberg, Nahum
MiRNAs招募miRNA诱导的沉默复合体(MiRISC)，其中包括ArgAerte和GW182作为核心蛋白。GW182蛋白影响靶mRNAs的翻译抑制和去烯基化。然而，GW182介导的抑制的分子机制仍然不清楚。我们在这里证明了人GW182独立地与PAN2-PAN3和CCR4-非死烯基酶复合体相互作用。GW182与CCR4-NOT的相互作用是由两个新发现的系统发育保守基序介导的。虽然两个基序都足以与CCR4-NOT结合，但只有一个基序可以促进靶mRNAs的过程性去烯化。因此，GW182既是招募死烯基酶的平台，也是促进CCR4-NOT去除聚(A)尾巴的死烯基酶共激活子。
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.