The Ras/PKA signaling pathway of Saccharomyces cerevisiae exhibits a functional interaction with the Sin4p complex of the RNA polymerase II holoenzyme

Genetics. 2001 Sep;159(1):77-89. doi: 10.1093/genetics/159.1.77.


Saccharomyces cerevisiae cells enter into the G(0)-like resting state, stationary phase, in response to specific types of nutrient limitation. We have initiated a genetic analysis of this resting state and have identified a collection of rye mutants that exhibit a defective transcriptional response to nutrient deprivation. These transcriptional defects appear to disrupt the control of normal growth because the rye mutants are unable to enter into a normal stationary phase upon nutrient deprivation. In this study, we examined the mutants in the rye1 complementation group and found that rye1 mutants were also defective for stationary phase entry. Interestingly, the RYE1 gene was found to be identical to SIN4, a gene that encodes a component of the yeast Mediator complex within the RNA polymerase II holoenzyme. Moreover, mutations that affected proteins within the Sin4p module of the Mediator exhibited specific genetic interactions with the Ras protein signaling pathway. For example, mutations that elevated the levels of Ras signaling, like RAS2(val19), were synthetic lethal with sin4. In all, our data suggest that specific proteins within the RNA polymerase II holoenzyme might be targets of signal transduction pathways that are responsible for coordinating gene expression with cell growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Division
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Fungal Proteins / metabolism
  • Genes, ras / genetics*
  • Genotype
  • Mediator Complex
  • Mutation
  • Phenotype
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA / metabolism
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction*
  • Time Factors
  • Trans-Activators*
  • Transcription, Genetic
  • ras Proteins / metabolism*


  • Fungal Proteins
  • Mediator Complex
  • SIN4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • RNA
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • RNA Polymerase II
  • ras Proteins