Hunting for Prions: Using Meiotic Inheritance Patterns to Attribute Epigenetic States to Prion Proteins

Mikala Capage, Jacob Evarts, and Dr. David Garcia, Institute of Molecular Biology, University of Oregon, 1318 Franklin Blvd, Room 272 Onyx, Eugene OR, 97401

Prion proteins, although commonly associated with neurodegenerative diseases, are not universally harmful to cells. Instead, prions, acting as an epigenetic mechanism, may allow cells to alter their phenotype in response to adverse environmental conditions. Importantly, prions are not dependent on chromosomal segregation and can be inherited into all meiotic progeny, instead of in the 2:2 pattern associated with genetic mutations. Although prions can naturally arise, de novo prion formation can be increased by transiently overexpressing the gene that encodes for the prion protein. The Garcia Lab recently screened RNA modifying enzymes for their potential to induce prion conformations. From this screen, six RNA modifying enzymes, Abd1, Cet1, Ppm2, Pus4, Pus6, and Trm5, exhibited higher maximum growth rates than control strains when exposed to adverse chemical stressors. It is now necessary to confirm that the heritable growth states are truly caused by a prion-based conformation of an RNA modifying enzyme. Here, a yeast tetrad sporulation and dissection protocol, along with growth assays, are employed to determine the patterns of dominance and of meiotic inheritance for the heritable growth states, to see if they match the dominance and 4:0 inheritance pattern of known prion proteins. These experiments found that 80% of the experimental diploid cells exhibited the same growth traits, indicating the growth trait is dominant. Additionally, growth assays indicate that sets of meiotic progenies from some of the strains show patterns of non-Mendelian inheritance, a strong indication that a prion is present in the cells. Taken together, these results are key in attributing the previously identified growth states to a prion conformation of an RNA modifying enzyme. The Garcia lab will continue to investigate these putative prions in future experiments. This research represents an important contribution to our understanding of epigenetic mechanisms and their effects on key cell processes.

Additional Abstract Information

Presenter: Mikala Capage

Institution: University of Oregon

Type: Poster

Subject: Biology

Status: Approved

Time and Location

Session: Poster 3
Date/Time: Mon 4:30pm-5:30pm
Session Number: 3055