Visualization of translation reorganization upon persistent ribosome collision stress in mammalian cells.
Visualization of translation reorganization upon persistent ribosome collision stress in mammalian cells.
复制标题
哺乳动物细胞中持续核糖体碰撞应激下翻译重组的可视化。
DOI：
10.1016/j.molcel.2024.01.015
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发表时间：
2024
期刊：
影响因子：
16
通讯作者：
Förster,Friedrich
中科院分区：
文献类型：
--
作者：
Fedry,Juliette;Silva,Joana;Vanevic,Mihajlo;Fronik,Stanley;Mechulam,Yves;Schmitt,Emmanuelle;desGeorges,Amédée;Faller,WilliamJames;Förster,Friedrich
异常缓慢的核糖体会引发碰撞，这是一种引发质量控制、信号传导和翻译衰减的压力哨兵。虽然每一个碰撞反应都被孤立地研究过，但它们在细胞中重塑翻译的集体行动的净后果却知之甚少。在这里，我们应用冷冻电子断层扫描可视化翻译机器在哺乳动物细胞在持续的碰撞应力。我们发现，多聚核糖体被压缩，高达30%的核糖体在螺旋状多聚核糖体或碰撞的二聚体，其中一些是绑定到应力效应GCN 1。本机碰撞接口延伸超出thein vitro表征的40 S，包括L1茎和eEF2，可能有助于易位抑制。未解析的tRNA结合的80S和60S以及异常的40S构型的积累确定了碰撞响应中的潜在限制步骤。我们的工作提供了一个全球视野的翻译机制，以应对持续的碰撞和翻译动态原位定量分析的框架。
Aberrantly slow ribosomes incur collisions, a sentinel of stress that triggers quality control, signaling, and translation attenuation. Although each collision response has been studied in isolation, the net consequences of their collective actions in reshaping translation in cells is poorly understood. Here, we apply cryoelectron tomography to visualize the translation machinery in mammalian cells during persistent collision stress. We find that polysomes are compressed, with up to 30% of ribosomes in helical polysomes or collided disomes, some of which are bound to the stress effector GCN1. The native collision interface extends beyond thein vitro-characterized 40S and includes the L1 stalk and eEF2, possibly contributing to translocation inhibition. The accumulation of unresolved tRNA-bound 80S and 60S and aberrant 40S configurations identifies potentially limiting steps in collision responses. Our work provides a global view of the translation machinery in response to persistent collisions and a framework for quantitative analysis of translation dynamicsin situ.