Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae
Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae
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DOI：
10.1128/mcb.00799-14
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发表时间：
2014-11-01
影响因子：
5.3
通讯作者：
Rospert, Sabine
中科院分区：
文献类型：
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作者：
Chiabudini, Marco;Tais, Arlette;Rospert, Sabine
核糖体停滞是使细胞质量控制机制能够检测异常mRNA的重要事件。酿酒酵母Hbs 1-Dom 34和Ski 7是经典释放因子eRF 3-eRF 1的同源物，其识别停滞的核糖体，促进核糖体释放，并诱导异常mRNA的降解。多聚腺苷酸化不停止mRNA编码含有C-末端多聚赖氨酸片段的异常蛋白质，其由于与核糖体出口通道的静电相互作用而引起核糖体停滞。在这里，我们描述了一种新的机制，被称为提前翻译终止，它释放C-末端截短的翻译产物从核糖体停止在多聚赖氨酸片段。多聚赖氨酸合成过程中的提前终止被废除时，核糖体失速是由于核糖体蛋白Asc 1的情况下，防止。与此相反，提前终止增强时，一般翻译延长率降低。非常规终止事件独立于Hbs 1-Dom 34和Ski 7，但依赖于eRF 3。此外，提前终止多聚赖氨酸合成过程中强烈增加的情况下，核糖体结合的伴侣核糖体相关复合物（RAC）和SSB（SSB 1和SSB 2）。基于这些数据，我们提出了一个模型，其中eRF 3-eRF 1可以催化释放新生的多肽，即使核糖体A位点含有一个正义密码子时，翻译速率异常低。
Ribosome stalling is an important incident enabling the cellular quality control machinery to detect aberrant mRNA. Saccharomyces cerevisiae Hbs1-Dom34 and Ski7 are homologs of the canonical release factor eRF3-eRF1, which recognize stalled ribosomes, promote ribosome release, and induce the decay of aberrant mRNA. Polyadenylated nonstop mRNA encodes aberrant proteins containing C-terminal polylysine segments which cause ribosome stalling due to electrostatic interaction with the ribosomal exit tunnel. Here we describe a novel mechanism, termed premature translation termination, which releases C-terminally truncated translation products from ribosomes stalled on polylysine segments. Premature termination during polylysine synthesis was abolished when ribosome stalling was prevented due to the absence of the ribosomal protein Asc1. In contrast, premature termination was enhanced, when the general rate of translation elongation was lowered. The unconventional termination event was independent of Hbs1-Dom34 and Ski7, but it was dependent on eRF3. Moreover, premature termination during polylysine synthesis was strongly increased in the absence of the ribosome-bound chaperones ribosome-associated complex (RAC) and Ssb (Ssb1 and Ssb2). On the basis of the data, we suggest a model in which eRF3-eRF1 can catalyze the release of nascent polypeptides even though the ribosomal A-site contains a sense codon when the rate of translation is abnormally low.