Non-coding transcription and post-transcriptional mRNA regulation in quiescent Saccharomyces cerevisiae

Abstract

Quiescence is a conserved resting state, which is required for long-term survival. Quiescent cells, far from being inert, are poised to re-enter the mitotic cell cycle when conditions are appropriate. In this thesis, I analyzed the nascent transcriptome of quiescent budding yeast and found an increase in relative abundance of non-coding transcription compared to G1-arrested yeast. Analysis of the nascent and steady-state transcriptomes also revealed increased post-transcriptional regulation in quiescence compared to G1-arrested cells. To further understand the role of post-transcriptional regulation and non-coding transcripts in quiescence, I investigated the nuclear exosome-NNS pathway. This pathway is known to function in the regulation of non-coding transcripts in exponentially growing yeast. My work revealed that the nuclear exosome and NNS regulate over one thousand mRNAs in quiescent cells in addition to canonical non-coding RNA targets. RNA sequencing yeast from multiple time points revealed that the nuclear exosome functions in two distinct phases, one around the diauxic shift and the other later in quiescence entry. mRNAs regulated by the NNS-nuclear exosome pathway are enriched in functions such as protein synthesis, metabolism, cellular organization, and the cell cycle, underscoring the importance of this pathway in promoting cellular quiescence.