Details

Autor(en) / Beteiligte

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

Titel

Stress-Induced Translation Inhibition through Rapid Displacement of Scanning Initiation Factors

Ist Teil von

• Molecular cell, 2020-11, Vol.80 (3), p.470-484.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (eukaryotic initiation factor 4A [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 30 s, explaining the rapid translation shutdown, but mRNAs remained stable. Heat shock induced progressive loss of 5′ RNA binding by initiation factors over ∼16 min 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. [Display omitted] •A quantitative proteomic approach reveals global stress-induced changes in RNA binding•Translation shutdown is driven by rapid loss of mRNA binding by key initiation factors•Heat shock induces general mRNA degradation facilitated by Xrn1 All organisms live in continuously changing environments, and RNA-binding proteins are critically important in responding to resulting stresses. Bresson et al. followed both global and specific changes in RNA-protein interactions over short times following glucose starvation or heat shock. The results reveal mechanisms underlying translational control of gene expression during stress.