GSE138557
A Non-Amyloid Prion Particle that Activates a Heritable Gene Expression Program.
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. Overall design: Two biological replicates were analyzed for each of 4 conditions (two independent transient overexpression of VTS1 gene for wild type genotype, one 'no transient overexpression' control for wild-type genotype, one vts1 deletion genotype)