Ribosome Collision Is Critical for Quality Control during No-Go Decay.

Ribosome Collision Is Critical for Quality Control during No-Go Decay.
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DOI:
10.1016/j.molcel.2017.08.019
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发表时间:
2017-10-19
期刊:
影响因子:
16
通讯作者:
Zaher HS
Zaher HS
中科院分区:
生物学1区
文献类型:
--
作者:
Simms CL;Yan LL;Zaher HS

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不去衰变(NGD)是一种真核生物的质量控制机制,进化以科普翻译停滞。该过程的特点是由一个内切核酸裂解附近的失速序列,但机制的细节尚不清楚。我们对切割位点的分析表明,切割需要mRNA上的多个核糖体。我们还表明,记者窝藏失速序列附近的起始密码子,不能容纳多个核糖体,不受NGD。与我们的模型相一致,我们发现核糖体密度每mRNA和切割效率之间的负相关。此外,在体内促进全局核糖体碰撞导致核糖体蛋白的泛素化,这表明碰撞被细胞感知以启动下游质量控制过程。总的来说,我们的数据表明,NGD和随后的质量控制是由核糖体碰撞触发的。该模型提供了对质量控制过程的监管以及它们减少脱靶效应的方式的见解。
No-go decay (NGD) is a eukaryotic quality control mechanism that evolved to cope with translational arrests. The process is characterized by an endonucleolytic cleavage near the stall sequence, but the mechanistic details are unclear. Our analysis of cleavage sites indicates that cleavage requires multiple ribosomes on the mRNA. We also show that reporters harboring stall sequences near the initiation codon, which cannot accommodate multiple ribosomes, are not subject to NGD. Consistent with our model, we uncover an inverse correlation between ribosome density per mRNA and cleavage efficiency. Furthermore, promoting global ribosome collision in vivo resulted in ubiquitination of ribosomal proteins suggesting that collision is sensed by the cell to initiate downstream quality control processes. Collectively our data suggests that NGD and subsequent quality control are triggered by ribosome collision. This model provides insight into the regulation of quality control processes and the manner by which they reduce off target effects.
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