A non-proteolytic role for ubiquitin in deadenylation of MHC-I mRNA by the RNA-binding E3-ligase MEX-3C.
A non-proteolytic role for ubiquitin in deadenylation of MHC-I mRNA by the RNA-binding E3-ligase MEX-3C.
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DOI：
10.1038/ncomms9670
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发表时间：
2015-10-16
影响因子：
16.6
通讯作者：
Lehner PJ
中科院分区：
文献类型：
--
作者：
Cano F;Rapiteanu R;Sebastiaan Winkler G;Lehner PJ
蛋白质和信使核糖核酸周转的调节在许多细胞过程中是必不可少的。我们最近发现，泛素--传统上与蛋白质降解有关--通过新发现的RNA结合E3泛素连接酶家族的作用，直接调节mRNAs的降解。目前尚不清楚泛素是如何调节信使核糖核酸的衰退的。在这里，我们确定了泛素在调节死烯基化中的新作用，这是mRNA降解的初始步骤，通常也是限速步骤。Mex-3C是这个RNA结合泛素连接酶家族的典型成员，它与胞质去烯化复合体和泛素化Cnot7(CAF1)有关，Cnot7是CCR4-NOT去烯化机制的主要催化亚基。我们确定了泛素在调节MHC-I mRNA死烯基化中的新作用，因为MEX-3C泛素化Cnot7调节其死烯基化活性，并且是MHC-I mRNA降解所必需的。由于蛋白酶体和溶酶体抑制剂都不能挽救MEX-3C介导的MHC-I信使核糖核酸的降解，我们的发现提示泛素在调节信使核糖核酸降解中具有新的非蛋白水解性功能。MRNA去烯化是调节降解的第一步，是由CCR4-NOT和PAN2-PAN3复合体的作用所介导的。在这里，作者证明了RNA结合的E3泛素连接酶MEX-3C与CCR4-NOT复合体结合，并泛素化催化亚基Cnot7来调节其去烯化活性。
The regulation of protein and mRNA turnover is essential for many cellular processes. We recently showed that ubiquitin—traditionally linked to protein degradation—directly regulates the degradation of mRNAs through the action of a newly identified family of RNA-binding E3 ubiquitin ligases. How ubiquitin regulates mRNA decay remains unclear. Here, we identify a new role for ubiquitin in regulating deadenylation, the initial and often rate-limiting step in mRNA degradation. MEX-3C, a canonical member of this family of RNA-binding ubiquitin ligases, associates with the cytoplasmic deadenylation complexes and ubiquitinates CNOT7(Caf1), the main catalytic subunit of the CCR4-NOT deadenylation machinery. We establish a new role for ubiquitin in regulating MHC-I mRNA deadenylation as ubiquitination of CNOT7 by MEX-3C regulates its deadenylation activity and is required for MHC-I mRNA degradation. Since neither proteasome nor lysosome inhibitors rescued MEX-3C-mediated MHC-I mRNA degradation, our findings suggest a new non-proteolytic function for ubiquitin in the regulation of mRNA decay. mRNA deadenylation, the first step in regulated degradation, is mediated by the action of the CCR4-NOT and PAN2-PAN3 complexes. Here the authors show that the RNA-binding E3 ubiquitin-ligase MEX-3C associates with the CCR4-NOT complex and ubiquitinates the catalytic subunit CNOT7 to regulate its deadenylation activity.