Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation.
Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation.
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DOI：
10.1261/rna.060897.117
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Brandman O
中科院分区：
文献类型：
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作者：
Sitron CS;Park JH;Brandman O
在开放阅读框架内过早阻止蛋白质合成会引起一种保护性反应，从而降解不完整的新生链条。在这种反应中，滞留的80S核糖体被分成大亚基和小亚基，允许组装核糖体质量控制复合体(RQC)，该复合体针对新生的链进行降解。细胞如何在大量活跃翻译的多肽中识别受阻的新生链条，目前还知之甚少。我们系统地研究了酿酒酵母中新生链条的翻译、抑制和修饰，以表征捕获与RQC靶向相结合的步骤。我们重点分析了两个知之甚少的80S核糖体结合蛋白，Asc1和Hel2，以及我们在这里发现的该途径的一个新成分SLh1。我们发现，在缺乏Asc1、Hel2和Slh1的情况下，核糖体停滞序列上的过早停滞仍然强烈地发生。然而，这三个因素是RQC修改新生链条所必需的。我们认为Asc1、Hel2和SLh1靶向阻止核糖体，并且这个靶向事件是RQC参与不完整的新生链并促进其降解的先决条件。
Premature arrest of protein synthesis within the open reading frame elicits a protective response that degrades the incomplete nascent chain. In this response, arrested 80S ribosomes are split into their large and small subunits, allowing assembly of the ribosome quality control complex (RQC), which targets nascent chains for degradation. How the cell recognizes arrested nascent chains among the vast pool of actively translating polypeptides is poorly understood. We systematically examined translation arrest and modification of nascent chains in Saccharomyces cerevisiae to characterize the steps that couple arrest to RQC targeting. We focused our analysis on two poorly understood 80S ribosome-binding proteins previously implicated in the response to failed translation, Asc1 and Hel2, as well as a new component of the pathway, Slh1, that we identified here. We found that premature arrest at ribosome stalling sequences still occurred robustly in the absence of Asc1, Hel2, and Slh1. However, these three factors were required for the RQC to modify the nascent chain. We propose that Asc1, Hel2, and Slh1 target arresting ribosomes and that this targeting event is a precondition for the RQC to engage the incomplete nascent chain and facilitate its degradation.