Timing of transcription controls the selective translation of newly synthesized mRNAs during acute environmental stress

Upon acute stress, cells switch from pro-growth to stress-responsive gene expression programs to promote adaptation, by mounting rapid transcriptonal and translational responses. How these parallel responses are coordinated to selectively switch gene expression is poorly understood. Here, we show that following acute glucose withdrawal, yeast cells do not first degrade its old, pro-growth mRNA that was produced before stress, or sequester them in microscopic P bodies, but rapidly represses their translation followed by accelerated decay. Transcriptional induction of an mRNA during stress is sufficient to escape translational repression. This suggests a model where cells can switch between gene expression programs by repressing the translation of old mRNA while providing preferred access for new mRNA to translation. This timing-controlled mechanism provides a general framework for rapid and selective regulation of gene expression in a sequence-independent fashion by elegant coordination of gene expression changes in the nucleus and cytoplasm. Overall design: We performed RNA-seq analysis of total mRNA levels, as well as ribosome footprints, to analyze changes in mRNA abundance and translation following acute glucose withdrawal of yeast cells. We further quantified polysomes enrichment for an inducible reporter as well as endogenous transcripts following acute glucose withdrawal. In addition, we performed SLAM-seq for pulse chase analysis of mRNA decay in the presence or absence of glucose, and for analysis of polysomes enrichment of newly-made mRNA under glucose withdrawal conditions.