Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases
Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases
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DOI：
10.1101/gad.1597707
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发表时间：
2007-12-01
影响因子：
10.5
通讯作者：
Hoshino, Shin-ichi
中科院分区：
文献类型：
--
作者：
Funakoshi, Yuji;Doi, Yusuke;Hoshino, Shin-ichi
在真核生物中，T-poly（A）尾的缩短是大多数mRNA降解的限速步骤，并且两种主要的mRNA去腺苷酸酶复合物-Caf 1-Ccr 4和Pan 2-Pan 3-在此过程中发挥核心作用，称为去腺苷酸化。然而，触发去腺苷化的分子机制仍然难以捉摸。以前，我们证明了真核细胞释放因子eRF 3介导的脱氧腺苷化和衰变的mRNA的方式耦合到翻译终止。在这里，我们报告的mRNA去腺苷化的机制。eRF 3介导的去腺苷化由Caf 1-Ccr 4和Pan 2-Pan 3催化。有趣的是，翻译终止复合物eRF 1-eRF 3、Pan 2-Pan 3和Caf 1-Ccr 4与多聚腺苷酸结合蛋白PABPC 1竞争性相互作用。在每种复合物中，eRF 3、Pan 3和Tob分别介导PABPC 1结合，并且PAM 2基序和PABC结构域的组合通常用于它们的接触。在PABPC 1上发生eRF 1-eRF 3与去腺苷酶的依赖性交换，因此，PABPC 1结合导致Pan 2-Pan 3和Caf 1-Ccr 4的活化。从这些结果，我们提出了一种机制，mRNA deadenylation的Pan 2-Pan 3和Caf 1-Ccr 4的合作与eRF 3和PABPC 1。
In eukaryotes, shortening of the T-poly(A) tail is the rate-limiting step in the degradation of most mRNAs, and two major mRNA deadenylase complexes-Caf1-Ccr4 and Pan2-Pan3-play central roles in this process, referred to as deadenylation. However, the molecular mechanism triggering deadenylation remains elusive. Previously, we demonstrated that eukaryotic releasing factor eRF3 mediates deadenylation and decay of mRNA in a manner coupled to translation termination. Here, we report the mechanism of mRNA deadenylation. The eRF3-mediated deadenylation is catalyzed by both Caf1-Ccr4 and Pan2-Pan3. interestingly, translation termination complexes eRF1-eRF3, Pan2-Pan3, and Caf1-Ccr4 competitively interact with polyadenylate-binding protein PABPC1. In each complex, eRF3, Pan3, and Tob, respectively, mediate PABPC1 binding, and a combination of a PAM2 motif and a PABC domain is commonly utilized for their contacts. A translation-dependent exchange of eRF1-eRF3 for the deadenylase occurs on PABPC1, Consequently, PABPC1 binding leads to the activation of Pan2-Pan3 and Caf1-Ccr4. From these results, we suggest a mechanism of mRNA deadenylation by Pan2-Pan3 and Caf1-Ccr4 in cooperation with eRF3 and PABPC1.