The activation of the decapping enzyme DCP2 by DCP1 occurs on the EDC4 scaffold and involves a conserved loop in DCP1.
The activation of the decapping enzyme DCP2 by DCP1 occurs on the EDC4 scaffold and involves a conserved loop in DCP1.
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DOI：
10.1093/nar/gku129
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发表时间：
2014-04
影响因子：
14.9
通讯作者：
Izaurralde E
中科院分区：
文献类型：
--
作者：
Chang CT;Bercovich N;Loh B;Jonas S;Izaurralde E
脱帽酶DCP2及其辅激活剂DCP1去除5 ' -帽结构，关闭翻译并使mRNA暴露于XRN1的5 ‘ -3 ’外溶降解。虽然酵母DCP1和DCP2直接相互作用，但另一个因子EDC4在后生动物中促进DCP1 - DCP2的结合。在这里，我们阐明了人类蛋白质如何相互作用来组装一个活跃的脱冠复合体，以及脱冠mrna如何被移交给XRN1。我们发现EDC4作为复合物组装的支架，为DCP1、DCP2和XRN1提供结合位点。DCP2和XRN1通过短线性motif （slms）同时结合到EDC4的c端结构域。此外，DCP1和DCP2在EDC4的促进下形成直接但弱的相互作用。突变和功能研究表明，DCP1和DCP2在EDC4支架上的对接是体内mRNA脱壳的关键步骤。他们还揭示了DCP1 EVH1结构域中含有天冬酰胺精氨酸的保守环（nr环）在DCP2激活中的关键作用。我们的数据表明，DCP1激活DCP2优先发生在EDC4支架上，这可能是DCP1激活DCP2与XRN1在人细胞中降解5 ‘到3 ’ mRNA的结合。
The removal of the 5′-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5′-to-3′ exonucleolytic degradation by XRN1. Although yeast DCP1 and DCP2 directly interact, an additional factor, EDC4, promotes DCP1–DCP2 association in metazoan. Here, we elucidate how the human proteins interact to assemble an active decapping complex and how decapped mRNAs are handed over to XRN1. We show that EDC4 serves as a scaffold for complex assembly, providing binding sites for DCP1, DCP2 and XRN1. DCP2 and XRN1 bind simultaneously to the EDC4 C-terminal domain through short linear motifs (SLiMs). Additionally, DCP1 and DCP2 form direct but weak interactions that are facilitated by EDC4. Mutational and functional studies indicate that the docking of DCP1 and DCP2 on the EDC4 scaffold is a critical step for mRNA decapping in vivo. They also revealed a crucial role for a conserved asparagine–arginine containing loop (the NR-loop) in the DCP1 EVH1 domain in DCP2 activation. Our data indicate that DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5′-to-3′ mRNA degradation by XRN1 in human cells.
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影响因子：
3.7
作者：
Bloch, Donald B.;Nobre, Rita A.;Yang, Wei-Hong
通讯作者：
Yang, Wei-Hong
影响因子：
16.8
作者：
Braun, Joerg E.;Truffault, Vincent;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa
影响因子：
16
作者：
Jinek M;Coyle SM;Doudna JA
通讯作者：
Doudna JA
影响因子：
3
作者：
Diebold, Marie-Laure;Fribourg, Sebastien;Romier, Christophe
通讯作者：
Romier, Christophe
DOI：
10.1073/pnas.1113620109
发表时间：
2012-02-21
影响因子：
11.1
作者：
Floor, Stephen N.;Borja, Mark S.;Gross, John D.
通讯作者：
Gross, John D.