How cells differentiate between old and new: newly synthesized mRNAs selectively escape translational repression following acute stress

When cells encounter changing conditions or environmental stress, they rapidly mount an adaptive response, for example by switching from pro-growth to stress-responsive gene expression programs. It is poorly understood how cells selectively silence pre-existing, pro- growth transcripts, yet efficiently translate transcriptionally-induced stress mRNA, and whether these transcriptional and post-transcriptional responses are coordinated. Using budding yeast as a model system, we could demonstrate that pre-existing mRNAs are not first degraded to halt protein synthesis, nor are they sequestered away in large biomolecular condensates such as P- bodies. Rather, their translation is rapidly repressed through a sequence-independent mechanism that differentiates between mRNAs produced before and after stress followed by their decay. Transcriptional induction of endogenous transcripts and reporter mRNAs during stress is sufficient to escape translational repression, while induction prior to stress leads to repression. Our results reveal a timing-controlled coordination of the transcriptional and translational responses in the nucleus and cytoplasm ensuring a rapid and widescale reprogramming of gene expression following rapid and large-scale changes in gene expression.