Work

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

Year: 2025

Type: article

Abstract: When cells encounter environmental stress, they rapidly mount an adaptive response 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. Here, we show that following acute glucose withdrawal in S. cerevisiae, pre-existing mRNAs are not first degraded to halt protein synthesis, nor are they sequestered away in 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 environmental stress.

Source: Molecular Cell

DOI: 10.1016/j.molcel.2025.11.004