Protein degradation and dynamic tRNA thiolation fine-tune translation at elevated temperatures

Maintenance of protein quality control has implications in various processes such as neurodegeneration and ageing. To investigate how environmental insults affect this process, we analysed the proteome of yeast continuously exposed to mild heat stress. In agreement with previous transcriptomics studies, amongst the most marked changes, we found up-regulation of cytoprotective factors; a shift from oxidative phosphorylation to fermentation; and down-regulation of translation. Importantly, we also identified a novel, post-translationally controlled, component of the heat shock response. The abundance of Ncs2p and Ncs6p, two members of the URM1 pathway responsible for the thiolation of wobble uridines in cytoplasmic tRNAs tKUUU, tQUUG and tEUUC, is down-regulated in a proteasomal dependent fashion. Using random forests we show that this results in differential translation of transcripts with a biased content for the corresponding codons. We propose that the role of this pathway in promoting catabolic and inhibiting anabolic processes, affords cells with additional time and resources needed to attain proper protein folding under periods of stress.

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