Multi-kinase control of environmental stress responsive transcription

Abstract

Cells respond to changes in environmental conditions by activating signal transduction pathways and gene expression programs. Here we present a dataset to explore the relationship between environmental stresses, kinases, and global gene expression in yeast. We subjected 28 drug-sensitive kinase mutants to 10 environmental conditions in the presence of inhibitor and performed mRNA deep sequencing. With these data, we reconstructed canonical stress pathways and identified examples of crosstalk among pathways. The data also implicated numerous kinases in novel environment-specific roles. However, rather than regulating dedicated sets of target genes, individual kinases tuned the magnitude of induction of the environmental stress response (ESR)-a gene expression signature shared across the set of perturbations-in environment-specific ways. This suggests that the ESR integrates inputs from multiple sensory kinases to modulate gene expression and growth control. As an example, we provide experimental evidence that the high osmolarity glycerol pathway is an upstream negative regulator of protein kinase A, a known inhibitor of the ESR. These results elaborate the central axis of cellular stress response signaling.

Performing in spite of starvation: How Saccharomyces cerevisiae maintains robust growth when facing famine zones in industrial bioreactors

“…Transcriptome analysis revealed added regulatory rearrangements that point towards a preference for PKA activity over TORC1 control. Down‐regulation of non‐relevant stress signalling cascades was observed, such as the osmo‐responsive MAPK cascade—a constitutive inhibitor of PKA (Mace et al, 2020 ). In terms of energy homeostasis, elevated translational capacity is ATP‐costly and might have contributed to the increased AEC difference during the LSL transition in DS.…”

Modeling single-cell phenotypes links yeast stress acclimation to transcriptional repression and pre-stress cellular states

“…On the other hand, the two factors could differ substantially in upstream regulation. Many signaling pathways have been implicated in Msn2 regulation, even during the same response (Mayordomo et al 2002;; Lee et al 2013;; Chasman et al 2014;; Gutin et al 2015;; Gutin et al 2019;; Mace et al 2020);; whether these pathways also regulate Dot6 is not known. In contrast, we found that Dot6 nuclear translocation before NaCl addition was significantly correlated in cells in the same colony, but Msn2 behavior may reflect subtle distinctions in cellular states, and these distinctions influence the subsequent stress response.…”

Protein kinase A controls yeast growth in visible light

“…5 c), both being consistent with at the most limited PKA activation, this can only be part of the explanation. Interestingly, using global transcriptomic analysis and chemical inhibition of alleles of the Pbs2 and Tpk1/2/3 kinases, antagonistic regulation of HOG and PKA-dependent targets under a wide variety of different stress conditions was recently reported [ 70 ]. The observation that Tpk1/2/3 inhibition appeared to be epistatic to Pbs2-deficiency for inducing the Msn2/4 target HSP12 was taken as evidence for HOG signaling negatively regulating PKA.…”