Translation-independent inhibition of mRNA deadenylation during stress in Saccharomyces cerevisiae

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Abstract
Post-transcriptional control mechanisms play an important role in regulating gene expression during cellular responses to stress. For example, many stresses inhibit translation, and at least some stresses inhibit mRNA turnover in yeast and mammalian cells. We show that hyperosmolarity, heat shock, and glucose deprivation stabilize multiple mRNAs in yeast, primarily through inhibition of deadenylation. Although these stresses inhibit translation and promote the movement of mRNAs into P-bodies, we also observed inhibition of deadenylation in cycloheximide-treated cells as well as in a mutant strain where translation initiation is impaired. This argues that inhibition of poly(A)-shortening is independent of the translational state of the mRNAs and can occur when mRNAs are localized in polysomes or are not engaged in translation. Analysis of pan2Δ or ccr4Δ strains indicates that stress inhibits the function of both the Ccr4p/Pop2p/Notp and the Pan2p/Pan3p deadenylases. We suggest that under stress, simultaneous repression of translation and deadenylation allows cells to selectively translate mRNAs specific to the stress response, while retaining the majority of the cytoplasmic pool of mRNAs for later reuse and recovery from stress. Moreover, because various cellular stresses also inhibit deadenylation in mammalian cells, this mechanism is likely to be a conserved aspect of the stress response.