A prion accelerates proliferation at the expense of lifespan

eLife

Edgar A Campbell¹  Christopher M Jakobson¹  Daniel F Jarosz²  David M Garcia³  Mitsuhiro Tsuchiya⁴  Matt Kaeberlein⁴  Ethan A Shaw⁵  Acadia L DiNardo⁵ 

[1] Department of Chemical & Systems Biology, Stanford University School of Medicine, Stanford, United States;Department of Chemical & Systems Biology, Stanford University School of Medicine, Stanford, United States;Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States;Department of Chemical & Systems Biology, Stanford University School of Medicine, Stanford, United States;Institute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United States;Department of Pathology, University of Washington, Seattle, United States;Institute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United States;

关键词: prions;    aging;    cell size;    protein synthesis;    epigenetics;    RNA modification;    S. cerevisiae;   

DOI  :  10.7554/eLife.60917

来源: eLife Sciences Publications, Ltd

【 摘 要 】

In fluctuating environments, switching between different growth strategies, such as those affecting cell size and proliferation, can be advantageous to an organism. Trade-offs arise, however. Mechanisms that aberrantly increase cell size or proliferation—such as mutations or chemicals that interfere with growth regulatory pathways—can also shorten lifespan. Here we report a natural example of how the interplay between growth and lifespan can be epigenetically controlled. We find that a highly conserved RNA-modifying enzyme, the pseudouridine synthase Pus4/TruB, can act as a prion, endowing yeast with greater proliferation rates at the cost of a shortened lifespan. Cells harboring the prion grow larger and exhibit altered protein synthesis. This epigenetic state, [BIG+] (better in growth), allows cells to heritably yet reversibly alter their translational program, leading to the differential synthesis of dozens of proteins, including many that regulate proliferation and aging. Our data reveal a new role for prion-based control of an RNA-modifying enzyme in driving heritable epigenetic states that transform cell growth and survival.

【 授权许可】

CC BY