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bioRxiv · 10.1101/2022.09.12.507689

The ribosome quality control factors Asc1 and Hel2 regulate the expression of HSP70 during heat shock and recovery

Boopathy, L. R. A.·Beadle, E.·Xiao, A.·Rico, A. G.-B.·Alecki, C.·Garcia de Andres, I.·Vera, M.
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Abstract

Cells rapidly adapt to survive harsh environmental conditions through the potent upregulation of molecular chaperones or heat shock proteins (HSPs). The inducible members of the HSP70 family are the fastest and most transcriptionally induced chaperone upon stress. The HSP70 mRNA life cycle regulation in the cytoplasm is unique because it is translated during stress when general translation is repressed and rapidly degraded once conditions are optimal for growth. Contrary to the role of the HSP70 mRNA 5 untranslated region in maximizing the synthesis of HSP70, we discovered that the coding sequence (CDS) represses its translation through the ribosome quality control (RQC) mechanism. The CDS of the most inducible HSP70 in Saccharomyces cerevisiae, SSA4, is uniquely biased with low-frequency codons that promote ribosome stalling during heat stress. The stalled ribosomes are recognized by RQC components Asc1p and Hel2p and two ribosome proteins, Rps28A and Rps19B, that we identified as new RQC components. Surprisingly, RQC does not signal the degradation of the SSA4 mRNA by no-go-decay (NGD). Instead, Asc1p destabilizes the SSA4 mRNA during recovery from heat stress by a mechanism independent of its ribosome binding and SSA4 CDS codon optimality. Therefore, Asc1p operates two synergistic mechanisms that converge to regulate the life cycle of HSP70 mRNA during stress and recovery. Our research identifies Asc1p as a critical regulator of the stress response and RQC as the system tuning HSP70 synthesis.

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Boopathy, L. R. A., Beadle, E., Xiao, A., Rico, A. G.-B., Alecki, C., Garcia de Andres, I., Vera, M.. 2022-09-13. The ribosome quality control factors Asc1 and Hel2 regulate the expression of HSP70 during heat shock and recovery. https://doi.org/10.1101/2022.09.12.507689

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