Sodium-induced GCN4 expression controls the accumulation of the 5' to 3' RNA degradation inhibitor, 3'-phosphoadenosine 5'-phosphate.

Most cytoplasmic mRNAs are decapped and digested by the 5'-3'-exonuclease Xrn1p in Saccharomyces cerevisiae. The activity of Xrn1p is naturally inhibited in the presence of 3'-phosphoadenosine 5'-phosphate (pAp), a metabolite produced during sulfate assimilation that is quickly metabolized to AMP by the enzymatic activity of Hal2p. However, pAp accumulates and 5'-3' degradation decreases in the presence of ions known to inhibit Hal2p activity, such as sodium or lithium. We have shown that yeast cells can better adapt to the presence of sodium than lithium because of their ability to reduce pAp accumulation by activating HAL2 expression in a Gcn4p-dependent response, a regulatory loop that is likely to be conserved in different yeast species. We have thus identified a new role for the transcriptional activity of Gcn4p in maintaining an active mRNA degradation pathway under conditions of sodium stress. Since deregulation of proteins involved in different metabolic pathways is observed in xrn1Delta mutants, the maintenance of mRNA degradation capacity is likely to be important for the accurate and rapid adaptation of gene expression to salt stress.