Interaction of the La-related protein Slf1 with colliding ribosomes maintains translation of oxidative-stress responsive mRNAs

In response to oxidative stress cells reprogram gene expression to enhance levels of antioxidant enzymes and promote survival. In Saccharomyces cerevisiae the polysome-interacting La-related proteins (LARPs) Slf1 and Sro9 aid adaptation of protein synthesis during stress by undetermined means. To gain insight in their mechanisms of action in stress responses, we determined LARP mRNA binding positions in stressed and unstressed cells. Both proteins bind within coding regions of stress-regulated antioxidant enzyme and other highly translated mRNAs in both optimal and stressed conditions. LARP interaction sites are framed and enriched with ribosome footprints suggesting ribosome-LARP-mRNA complexes are identified. Although stress-induced translation of antioxidant enzyme mRNAs is attenuated in slf1 Delta, these mRNAs remain on polysomes. Focusing further on Slf1, we find it binds to both monosomes and disomes following RNase treatment. slf1 Delta reduces disome enrichment during stress and alters programmed ribosome frameshifting rates. We propose that Slf1 is a ribosome-associated translational modulator that stabilises stalled/collided ribosomes, prevents ribosome frameshifting and so promotes translation of a set of highly-translated mRNAs that together facilitate cell survival and adaptation to stress. [Graphics] .

Automated summary

Cells respond to oxidative stress by reprogramming gene expression to enhance levels of antioxidant enzymes. In Saccharomyces cerevisiae, proteins Slf1 and Sro9 play a role in protein synthesis adaptation during stress. Slf1 is identified as a ribosome-associated translational modulator that promotes translation of highly-translated mRNAs, facilitating cell survival and adaptation to stress.