Seidler, J.;Dalwig, J.;Graumann, J.;Straesser, K.

SUMMARY The ability to adapt to changing environmental conditions is essential for cellular survival. A central feature of the eukaryotic stress response is the inhibition of bulk mRNA nuclear export, while stress-induced transcripts are specifically exported. However, the molecular mechanisms that simultaneously inhibit bulk mRNA export while mediating selective export of specific transcripts remain poorly understood. Here, we performed comparative phosphoproteomic analyses of S. cerevisiae under different stress conditions. We identified a heat shock-induced increase in phosphorylation within the N-terminal domain of the mRNA export adaptor Yra1. Preventing this phosphorylation significantly reduces nuclear accumulation of poly(A) + RNA during heat stress and concomitantly enhances the export of heat-induced transcripts. Mechanistically, Yra1 phosphorylation appears to weaken its interaction with the export receptor Mex67, thereby contributing to nuclear accumulation of bulk poly(A) + RNA under heat stress. Together, our findings establish Yra1 phosphorylation as a previously unrecognized regulatory mechanism that promotes nuclear mRNA accumulation during heat stress and contributes to selective mRNA export.