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

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 pan2D or ccr4D 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.

Formation of Cytoplasmic P-Bodies inSakeYeast during JapaneseSakeBrewing and Wine Making

“…4,20) Here we found that ethanol stress also enhanced the formation of P-bodies in sake yeast as well as laboratory strains in SD medium (Fig. 1A), and that elimination of the ethanol rapidly caused the disassembly of P-bodies (Fig.…”

CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation

“…For example, both nuclear pre-mRNA and cytoplasmic mRNA polyadenylation can be regulated during the cell cycle (Colgan et al 1996;Groisman et al 2006) and in response to certain signaling events (Wu et al 1998;Mellman et al 2008). Moreover, poly(A) dynamics are also regulated by environmental stress (Hilgers et al 2006) and by miRNAs (Wu et al 2006). We speculate that CPEB activity may be necessary for maintaining steady state p53 levels under normal conditions where it has important functions in cellular aging and energy metabolism (Bensaad and Vousden 2007).…”

The transcriptional inhibitor thiolutin blocks mRNA degradation in yeast

“…It has been shown that thiolutin induces some stress in yeast cells (Grigull et al, 2004) and that stress induces mRNA stabilization (reviewed in Bond, 2006). However, the stress stabilization of mRNA occurs by inhibition of deadenylation (Hilgers et al, 2006), hence the effect of thiolutin cannot be an indirect consequence of the stress. Thiolutin also has an inhibitory effect on translation at high concentrations (Jiménez et al, 1973) and it is known that inhibition of translation blocks mRNA degradation at the level of decapping, without inhibiting deadenlylation (Beelman and Parker, 1994).…”