Stress-induced translation inhibition through rapid displacement of scanning initiation factors

Stefan Bresson, Vadim Shchepachev, Christos Spanos, Tomasz Turowski, Juri Rappsilber, David Tollervey

Research output: Contribution to journalArticlepeer-review

Abstract

Cellular responses to environmental stress are frequently mediated by RNA-binding proteins(RBPs). Here, we examined global RBP dynamics in Saccharomyces cerevisiae in response to glucose starvation and heat shock. Each stress induced rapid remodeling of the RNA-protein interactome, without corresponding changes in RBP abundance. Consistent with general translation shutdown, ribosomal proteins contacting the mRNA showed decreased RNA association. Among translation components, RNA-association was most reduced for initiation factors involved in 40S scanning (eIF4A, eIF4B, and Ded1), indicating a common mechanism of translational repression. In unstressed cells, eIF4A, eIF4B, and Ded1 primarily targeted the 5′-ends of mRNAs. Following glucose withdrawal, 5’-binding was abolished within 30sec,explaining the rapid translation shutdown, but mRNAs remained stable. Heat shock induced progressive loss of 5’ RNA-binding by initiation factors over ~16min and provoked mRNA degradation, particularly for translation-related factors, mediated by Xrn1. Taken together, these results reveal mechanisms underlying translational control of gene expression during stress.
Original languageEnglish
Pages (from-to)470-484.e8
Number of pages15
JournalMolecular Cell
Volume80
Issue number3
Early online date13 Oct 2020
DOIs
Publication statusPublished - 5 Nov 2020

Keywords

  • protein-RNA interaction
  • RNA binding sites
  • UV crosslinking
  • mass spectometry
  • yeast
  • stress responses

Fingerprint

Dive into the research topics of 'Stress-induced translation inhibition through rapid displacement of scanning initiation factors'. Together they form a unique fingerprint.

Cite this