Genetic screen of the yeast environmental stress response dynamics uncovers distinct regulatory phases

Jenia Gutin, Daphna Joseph-Strauss, Amit Sadeh, Eli Shalom, Nir Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Cells respond to environmental fluctuations by regulating multiple transcriptional programs. This response can be studied by measuring the effect of environmental changes on the transcriptome or the proteome of the cell at the end of the response. However, the dynamics of the response reflect the working of the regulatory mechanisms in action. Here, we utilized a fluorescent stress reporter gene to track the dynamics of protein production in yeast responding to environmental stress. The response is modulated by changes in both the duration and rate of transcription. We probed the underlying molecular pathways controlling these two dimensions using a library of ~1,600 single- and double-mutant strains. Dissection of the effects of these mutants and the interactions between them identified distinct modulators of response duration and response rate. Using a combination of mRNA-seq and live-cell microscopy, we uncover mechanisms by which Msn2/4, Mck1, Msn5, and the cAMP/PKA pathway modulate the response of a large module of stress-induced genes in two discrete regulatory phases. Our results and analysis show that transcriptional stress response is regulated by multiple mechanisms that overlap in time and cellular location.

Original languageAmerican English
Article numbere8939
JournalMolecular Systems Biology
Volume15
Issue number8
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 The Authors. Published under the terms of the CC BY 4.0 license

Keywords

  • Msn2 and Msn4
  • budding yeast
  • dynamics of transcriptional response to stress
  • genetic interactions
  • signaling pathways

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