Department of Biochemistry, McGill University, Montreal, Canada.
Nat Struct Mol Biol. 2011 Oct 7;18(11):1211-7. doi: 10.1038/nsmb.2149.
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.
miRNAs 招募 microRNA 诱导的沉默复合物 (miRISC)，该复合物包括 Argonaute 和 GW182 作为核心蛋白。GW182 蛋白对靶 mRNAs 进行翻译抑制和去腺苷酸化。然而，GW182 介导的抑制的分子机制仍不清楚。我们在这里表明，人类 GW182 可独立与 PAN2-PAN3 和 CCR4-NOT 脱腺苷酸酶复合物相互作用。GW182 与 CCR4-NOT 的相互作用由两个新发现的系统发育保守基序介导。尽管两个基序都足以结合 CCR4-NOT，但只有其中一个可以促进靶 mRNAs 的连续去腺苷酸化。因此，GW182 既是招募脱腺苷酸酶的平台，也是促进 CCR4-NOT 去除 poly(A) 尾巴的脱腺苷酸酶共激活因子。
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