Netherlands Organisation for Scientific Research (NWO)
724016001
オランダ
Netherlands Organisation for Scientific Research (NWO)
212152
オランダ
引用
ジャーナル: Mol Cell / 年: 2024 タイトル: Visualization of translation reorganization upon persistent ribosome collision stress in mammalian cells. 著者: Juliette Fedry / Joana Silva / Mihajlo Vanevic / Stanley Fronik / Yves Mechulam / Emmanuelle Schmitt / Amédée des Georges / William James Faller / Friedrich Förster / 要旨: 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, ...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 the in 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 dynamics in situ.