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A non-proteolytic role for ubiquitin in deadenylation of MHC-I mRNA by the RNA-binding E3-ligase MEX-3C.
Nature Communications ( IF 14.7 ) Pub Date : 2015-Oct-16 , DOI: 10.1038/ncomms9670
Florencia Cano 1, 2 , Radu Rapiteanu 1 , G Sebastiaan Winkler 3 , Paul J Lehner 1
Affiliation  

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.

中文翻译:

泛素在 RNA 结合 E3 连接酶 MEX-3C 对 MHC-I mRNA 的去腺苷酸化中的非蛋白水解作用。

蛋白质和 mRNA 周转的调节对于许多细胞过程至关重要。我们最近表明,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 mRNA 的降解。泛素如何调节 mRNA 衰变仍不清楚。在这里,我们确定了泛素在调节去腺苷酸化中的新作用,这是 mRNA 降解的初始且通常是限速步骤。MEX-3C 是该 RNA 结合泛素连接酶家族的典型成员,它与细胞质去腺苷酸化复合物结合并泛素化 CNOT7(Caf1),这是 CCR4-NOT 去腺苷酸化机制的主要催化亚基。我们建立了泛素在调节 MHC-I mRNA 去腺苷酸化方面的新作用,因为 MEX-3C 对 CNOT7 的泛素化调节其去腺苷酸化活性并且是 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 mRNA 降解,我们的研究结果表明泛素在调节 mRNA 衰变中具有新的非蛋白水解功能。
更新日期:2015-10-19
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