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A Non-Amyloid Prion Particle that Activates a Heritable Gene Expression Program

82 Pages Posted: 15 Apr 2019 Sneak Peek Status: Under Review

See all articles by Anupam K. Chakravarty

Anupam K. Chakravarty

Stanford University - Department of Chemical and Systems Biology

Tina Smejkal

Stanford University - Department of Chemical and Systems Biology

Alan Itakura

Stanford University - Department of Biology

David M. Garcia

Stanford University - Department of Chemical and Systems Biology

Daniel F. Jarosz

Stanford University - Department of Chemical and Systems Biology; Stanford University - Department of Developmental Biology

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Abstract

Spatiotemporal gene regulation is often driven by RNA-binding proteins that harbor long intrinsically disordered regions in addition to folded RNA-binding domains. We report that the disordered region of the evolutionarily ancient developmental regulator Smaug drives selfassembly into gel-like condensates. These proteinaceous particles are not composed ofamyloid. Yet they are infectious, allowing them to act as a protein-based epigenetic element: a prion. In contrast to many amyloid prions, condensation of Smaug enhances its function in mRNA decay, and its self-assembly properties are conserved over large evolutionary distances. Yeast cells harboring the [SMAUG+] prion downregulate a coherent network of mRNAs and exhibit improved growth under nutrient limitation. Smaug condensates formed from purified protein can transform naïve cells to acquire the prion. Our data establish that non-amyloid selfassembly of RNA-binding proteins can drive a form of epigenetics beyond the chromosome, instilling adaptive gene expression programs that are heritable over long biological timescales.

Keywords: non-amyloid prion particle, Spatiotemporal gene

Suggested Citation

Chakravarty, Anupam K. and Smejkal, Tina and Itakura, Alan and Garcia, David M. and Jarosz, Daniel F., A Non-Amyloid Prion Particle that Activates a Heritable Gene Expression Program (April 14, 2019). Available at SSRN: https://ssrn.com/abstract=3371672 or http://dx.doi.org/10.2139/ssrn.3371672
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Anupam K. Chakravarty

Stanford University - Department of Chemical and Systems Biology

Stanford, CA 94305
United States

Tina Smejkal

Stanford University - Department of Chemical and Systems Biology

Stanford, CA 94305
United States

Alan Itakura

Stanford University - Department of Biology ( email )

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

David M. Garcia

Stanford University - Department of Chemical and Systems Biology

Stanford, CA 94305
United States

Daniel F. Jarosz (Contact Author)

Stanford University - Department of Chemical and Systems Biology ( email )

Stanford, CA 94305
United States

Stanford University - Department of Developmental Biology ( email )

Stanford, CA 94305
United States

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