Visualization of translation reorganization upon persistent ribosome collision stress in mammalian cells

Juliette Fedry*, Joana Silva, Mihajlo Vanevic, Stanley Fronik, Yves Mechulam, Emmanuelle Schmitt, Amédée des Georges, William James Faller, Friedrich Förster

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)1078-1089.e4
JournalMolecular Cell
Volume84
Issue number6
Early online date2 Feb 2024
DOIs
Publication statusPublished - 21 Mar 2024

Keywords

  • cryoelectron tomography
  • initiation
  • polysome
  • ribosome collision
  • ribosome quality control
  • translation regulation

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