Influence of a prion protein on the TOR pathway in Saccharomyces Cerevisiae

Abstract

Pseudouridine synthases are critical RNA modifiers in eukaryotes. One member of this family of enzymes, encoded by the Pus4 gene in the budding yeast Saccharomyces cerevisiae, forms a prion protein, named [BIG+]. Rather than resulting in cell death, as for known mammalian prion diseases, [BIG+] promotes increased cell proliferation and cell size. These observations raise the question of how the prion promotes cell growth. One possible mechanism is an alteration to a fundamental eukaryotic growth control pathway, mediated by the TOR complex (“target of rapamycin”). One target of TOR, a protein kinase, is Sch9, an AGC kinase, which is activated via phosphorylation by the TOR complex. Sch9 activity promotes multiple processes essential for growth such as ribosome biogenesis, translation control, and cAPK activity. To better understand the relationship between [BIG+] and the TOR pathway, we have introduced hyperactive mutants of TOR or Sch9 into [BIG+] and naïve (non-prion) cells. By monitoring growth rate in media with varying levels of arginine, we can monitor [BIG+] response to different nutrient conditions. We found that [BIG+] cells are resistant to perturbations that would normally alter the growth of cells through the TOR complex. This contributes to our understanding of how the prion and TOR complex are interacting to influence cell growth epigenetically.