Genetic interaction between glyoxylate pathway regulator UCC1 and La-motif-encoding SRO9 regulates stress response and growth rate improvement in Saccharomyces cerevisiae

J Biochem Mol Toxicol. 2021 Jul;35(7):e22781. doi: 10.1002/jbt.22781. Epub 2021 Apr 2.

Abstract

Nonavailability of glucose as a carbon source results in glyoxylate pathway activation, which metabolizes nonfermentable carbon for energy generation in Saccharomyces cerevisiae. Ucc1p of S. cerevisiae inhibits activation of the glyoxylate pathway by targeting Cit2p, a key glyoxylate enzyme for ubiquitin-mediated proteasomal degradation when glucose is available as a carbon source. Sro9p, a La-motif protein involved in RNA biogenesis, interacts physically with the messenger RNA of UCC1; however, its functional relevance is yet to be discovered. This study presents binary epistatic interaction between UCC1 and SRO9, with functional implication on the growth rate, response to genotoxic stress, resistance to apoptosis, and petite mutation. Cells with ucc1Δsro9Δ, as their genetic background, exhibit alteration in morphology, improvement in growth rate, resistance to apoptosis, and petite mutation. Moreover, the study indicates a cross-link between ubiquitin-proteasome system and RNA biogenesis and metabolism, with applications in industrial fermentation and screening for cancer therapeutics.

Keywords: E3 ligase; F-box motif; apoptosis; petite mutation; stress.

MeSH terms

  • Glyoxylates / metabolism*
  • Microfilament Proteins* / genetics
  • Microfilament Proteins* / metabolism
  • RNA, Fungal* / genetics
  • RNA, Fungal* / metabolism
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / growth & development

Substances

  • Glyoxylates
  • Microfilament Proteins
  • RNA, Fungal
  • RNA, Messenger
  • RNA-Binding Proteins
  • SRO9 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • glyoxylic acid