RNA Modifying Enzymes with Prion-Like Properties
We place particular focus on regulators of RNA chemical modifications, or RNA modifying enzymes (RMEs), due to their ability to influence expression of numerous genes simultaneously, through molecularly definable rules. Through a large phenotypic screen, based on transient perturbation of more than seventy RMEs and two-dozen other RBPs, that generated >3.5 million growth data points, we discovered numerous examples of RMEs driving prion-like, heritable growth states. These states influenced fundamental traits such as proliferation, cell size, lifespan, and growth in a variety of stresses. Our goals are to understand the causes and effects of this type of regulation, by connecting long-lasting, heritable changes in RNA regulation to their consequent effects on cell growth across varying environments.
Live Fast, Die Young—An Ancient RNA Modifying Enzyme Accelerating Proliferation and Aging
We have studied one particular example of an RME that can promote a prion-like epigenetic state in great detail. This state causes yeast to proliferate, and age, rapidly. Compared to genetically identical "naive" cells, these cells, represented by a state we call [BIG+], are larger in size, have increased protein synthesis, and have an altered response to TOR pathway inhibition. This state thus provides a means by which cells can epigenetically and reversibly adopt different proliferation and aging programs. We are exploring the molecular basis of this state, in particular its effects on protein synthesis, as well as its existence beyond yeast.
Thanks to these organizations for supporting our research:
National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) [2021–2026]
The Donald E. and Delia B. Baxter Foundation [2020–2021]
The Medical Research Foundation of Oregon [2019–2020]
The University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging [2019–2020]
University of Oregon