Hunting for Prions: Propagating Putative Prion States in Budding Yeast

Abstract

Prions have been closely associated with fatal neurodegenerative diseases. Recent evidence, however, suggests that prions also represent an additional class of epigenetic mechanism that is biologically beneficial. From an evolutionary standpoint, the ability to change phenotypes without requiring changes to the genome, as prions do, would be hugely beneficial in fluctuating environments. Through overexpressing proteins and introducing environmental stressors, two techniques known to increase de novo prion formation, we performed a large-scale screen of many RNA-modifying enzymes in budding yeast to test if they harbor beneficial prionogenic behavior. From this screen, six induced prion-like states were found to be mitotically stable and infectious. We show that many of these putative prions are dominant and are dependent on chaperone proteins, which is consistent with a prion-based epigenetic mechanism. Prion-based inheritance is expanding on the central dogma of biology, contributing to the belief that prions work as an epigenetic mechanism for passing on heritable traits.