The interactions of GW182 proteins with PABP and deadenylases are required for both translational repression and degradation of miRNA targets.
The interactions of GW182 proteins with PABP and deadenylases are required for both translational repression and degradation of miRNA targets.
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DOI：
10.1093/nar/gks1078
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发表时间：
2013-01
影响因子：
14.9
通讯作者：
Izaurralde E
中科院分区：
文献类型：
--
作者：
Huntzinger E;Kuzuoglu-Öztürk D;Braun JE;Eulalio A;Wohlbold L;Izaurralde E
动物miRNAs通过翻译抑制、去烯基化和随后的mRNA降解来沉默mRNA靶标的表达。沉默需要miRNAs与ArgAerte蛋白和GW182家族蛋白相关联。反过来，GW182蛋白与聚(A)结合蛋白(PABP)以及PAN2-PAN3和CCR4-NOT死烯基酶复合体相互作用。这些相互作用是miRNA靶标的死烯化和衰变所必需的。最近的研究表明，miRNAs在诱导靶基因死烯基化和衰变之前抑制翻译；然而，翻译抑制和死烯基化是否是耦合的或代表独立的抑制机制尚不清楚。另一个剩下的问题是，翻译抑制是否也需要GW182蛋白与PABP和死烯基酶相互作用。为了解决这些问题，我们描述了果蝇GW182与死烯基酶的相互作用，并定义了功能GW182蛋白的最低要求。在黑腹果蝇和人类细胞中的功能分析表明，miRNA介导的翻译抑制和降解是机械联系的，并通过GW182蛋白与PABP和死烯基酶的相互作用而触发。
Animal miRNAs silence the expression of mRNA targets through translational repression, deadenylation and subsequent mRNA degradation. Silencing requires association of miRNAs with an Argonaute protein and a GW182 family protein. In turn, GW182 proteins interact with poly(A)-binding protein (PABP) and the PAN2–PAN3 and CCR4–NOT deadenylase complexes. These interactions are required for the deadenylation and decay of miRNA targets. Recent studies have indicated that miRNAs repress translation before inducing target deadenylation and decay; however, whether translational repression and deadenylation are coupled or represent independent repressive mechanisms is unclear. Another remaining question is whether translational repression also requires GW182 proteins to interact with both PABP and deadenylases. To address these questions, we characterized the interaction of Drosophila melanogaster GW182 with deadenylases and defined the minimal requirements for a functional GW182 protein. Functional assays in D. melanogaster and human cells indicate that miRNA-mediated translational repression and degradation are mechanistically linked and are triggered through the interactions of GW182 proteins with PABP and deadenylases.
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影响因子：
14.9
作者：
Petit AP;Wohlbold L;Bawankar P;Huntzinger E;Schmidt S;Izaurralde E;Weichenrieder O
通讯作者：
Weichenrieder O
影响因子：
56.9
作者：
Mayr, Christine;Hemann, Michael T.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
11.4
作者：
Huntzinger, Eric;Braun, Joerg E.;Heimstaedt, Susanne;Zekri, Latifa;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa
影响因子：
16.8
作者：
Moretti, Francesca;Kaiser, Constanze;Hentze, Matthias W.
通讯作者：
Hentze, Matthias W.
影响因子：
16.8
作者：
Fabian, Marc R.;Cieplak, Maja K.;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum