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

Research output: Contribution to journalArticle

Original languageEnglish
JournalMolecular Cell
Publication statusAccepted/In press - 21 Sep 2020

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.

    Research areas

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

ID: 165312532