Tollervey lab paper featured in Molecular Cell. Authors Image 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. Bresson, S., Shchepachev, V., Spanos, C., Turowski, T.W., Rappsilber, J., and Tollervey, D. Summary of Paper by Lori Koch Organisms must adapt to changes in their environment and this is especially critical for unicellular, immobile organisms such as budding yeast. Often, the response is to activate or silence the appropriate sets of genes and this can be accomplished by regulating many different steps in the process of gene expression. Slowing the rate of protein synthesis is one of the most rapid and dramatic changes that occur. In particular, the initiation of translation of mRNAs by RNA-binding proteins (RBPs) is a rate-limiting step. While factors essential for this process have been identified, the overall ‘rules’ that determine which proteins bind to which RNAs under stressed conditions are unknown. In addition, the unique mechanism by which yeast stop translation under stressed conditions was unclear. In their recent work published in Molecular Cell, postdoctoral scientist Stefan Bresson and his colleagues in the Tollervey and Rappsilber groups addressed these questions using comprehensive methods to map all protein-RNA interactions in the cell before and after the stresses of glucose withdrawal and heat shock. They employed a method developed in the Tollervey lab called TRAPP that involves an RNA purification followed by identification of associated proteins by mass spectrometry. This analysis revealed that a common group of translation initiation and scanning factors, including eIF4A, eIF4B, and Ded1, are lost from RNAs following both stress conditions. Glucose withdrawal changed protein-RNA interactions very rapidly, within 2 minutes, while changes to heat shock were more gradual but were significant by 16 minutes after exposure. Using a reciprocal method called CRAC to analyse RNAs associated with targeted proteins, they found that eIF4A and eIF4B both targeted a single site close to the start codon and many Ded1-associated RNAs followed the same pattern, but a significant proportion had Ded1 dispersed throughout the RNA. Remarkably, RNA association with these proteins dropped within 30 seconds of stress. Overall, the work reveals a detailed, time-resolved picture of stress-induced translation shutoff. It also provides a plethora of information for further studies on the nature and consequences of different protein-RNA interactions. Rleated links Journal Link Tollervey Lab Website DOI This article was published on 2024-06-17
