Misfolded but not Malicious: Prion Proteins in Budding Yeast

Prion proteins, although frequently associated with neurodegenerative diseases, are not universally harmful to cells. Instead, prions may serve as a beneficial epigenetic mechanism, allowing cells
to alter their phenotype to adapt to adverse environmental conditions. Prions form when a protein adopts alternate folding conformation. The Garcia Lab aims to identify beneficial prions using the budding yeast, Saccharomyces cerevisiae. We are particularly interested in prion conformations of RNA modifying enzymes (RMEs), because these proteins can affect the expression of many genes simultaneously. After screening hundreds of yeast strains, the Garcia Lab has identified six strains of yeast—associated with the RMEs Abd1, Cet1, Ppm2, Pus4, Pus6 and Trm5—that exhibit resistance to harmful chemicals . Extensive tests are needed to confirm that the resistance to stress is caused by a prion conformation of an RNA modifying enzyme. Here, data describing the meiotic inheritance, protein dependance, and cytoplasmic inheritance are presented. Taken together, these results are key in attributing the previously identified growth states to a prion conformation of each of the six RNA modifying enzymes . The Garcia lab will continue to investigate these putative prions in future experiments to determine the mechanism for resistance. This research represents an important contribution to our understanding of prions as a protein-based epigenetic mechanism and their effects on key cell processes.