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

Saccharomyces cerevisiae cells enter into the G.-like resting state, statio nary, phase, in response to specific types of nutrient limitation. We have initiated a genetic analysis of this resting state and have identified a co llection of rye mutants that exhibit a defective transcriptional response t o 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 exam ined the mutants in the rye1 complementation group and found that rye1 muta nts 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. Moreov er, mutations that affected proteins within the Sin4p module of the Mediato r exhibited specific genetic interactions with the Ras protein signaling pa thway. For example, mutations that elevated the levels of Ras signaling, li ke RAS2(eal19), were synthetic lethal with sin4. In all, our data suggest t hat specific proteins within the RNA polymerase if holoenzyme might be targ ets of signal transduction pathways that are responsible for coordinating g ene expression with cell growth.