Accelerated proliferation and aging driven by the prion state of an RNA-modifying enzyme
Abstract/Contents
- Abstract
- The term 'prion' is loaded with fear and negative connotation. The reason for this is because the first prions to be described, those of PrP in various species, were agents of death and disease unlike any known to mankind up to that point. The PrP prions captured the attention and fear of the general public and shaped our understanding of what prions are or could be for decades after. But prions can be more than just agents of disease, they can drive paradigm-shifting biology. If we go back to the original definition as coined by Stanley Prusiner himself, the only requirements to be a prion is to be proteinaceous and infectious. There are no thresholds of Q/N enrichments that need to be met or β- amyloid fibers formed in order to be considered a prion. Prions are highly stable protein conformations that can drive new biological phenotypes endowed with certain characteristics unique to prions. These phenotypes are usually dominant, disobey Mendel's law on inheritance, rely on protein chaperones for the faithful propagation across generations, and are encoded not in nucleic acid, but in the protein conformation itself. 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. 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.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Campbell, Edgar Alfred |
|---|---|
| Degree supervisor | Jarosz, Daniel |
| Thesis advisor | Jarosz, Daniel |
| Thesis advisor | Brunet, Anne, 1972- |
| Thesis advisor | Ferrell, James Ellsworth |
| Thesis advisor | Mochly-Rosen, Daria |
| Degree committee member | Brunet, Anne, 1972- |
| Degree committee member | Ferrell, James Ellsworth |
| Degree committee member | Mochly-Rosen, Daria |
| Associated with | Stanford University, Department of Chemical and Systems Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Edgar A. Campbell IV. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/kb398yp3057 |
Access conditions
- Copyright
- © 2021 by Edgar Alfred Campbell
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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