Post-transcriptional regulation shapes the transcriptome of quiescent budding yeast

To facilitate long-term survival, cells must exit the cell cycle and enter quiescence, a reversible non-replicative state. Budding yeast cells reprogram their gene expression during quiescence entry to silence transcription, but how the nascent transcriptome changes in quiescence is unknown. By investigating the nascent transcriptome, we identified over a thousand noncoding RNAs in quiescent and G1 yeast cells, and found noncoding transcription represented a larger portion of the quiescent transcriptome than in G1. Additionally, both mRNA and ncRNA are subject to increased post-transcriptional regulation in quiescence compared to G1. We found that, in quiescence, the nuclear exosome-NNS pathway suppresses over one thousand mRNAs, in addition to canonical noncoding RNAs. RNA sequencing through quiescent entry revealed two distinct time points at which the nuclear exosome controls the abundance of mRNAs involved in protein production, cellular organization, and metabolism, thereby facilitating efficient quiescence entry. Our work identified a previously unknown key biological role for the nuclear exosome-NNS pathway in mRNA regulation and uncovered a novel layer of gene-expression control in quiescence. Graphical Abstract

Automated summary

To ensure cell survival during quiescence, cells modulate their gene expression and transcription. By studying the nascent transcriptome, researchers identified over a thousand noncoding RNAs in quiescent and G1 yeast cells, revealing that noncoding transcription plays a larger role in the quiescent state. Furthermore, post-transcriptional regulation is increased in quiescence, affecting both mRNA and ncRNA. The nuclear exosome-NNS pathway was found to regulate the abundance of mRNAs involved in various cellular processes during quiescent entry, highlighting its important biological role in mRNA regulation.