An interchangeable prion-like domain is required for Ty1 retrotransposition

• Authors: Sean L. Beckwith, University of Georgia; Emily J. Nomberg, University of Georgia; Abigail C. Newman, University of Georgia; Jeannette V. Taylor, Emory University; Ricardo C. Guerrero, Emory University; David J. Garfinkel, University of Georgia
• Journal Title: bioRxiv
• Volume: Volume 2023
• Publisher: NIH | 2023-02-27
• Type of Work: Article | Preprint: Prior to Peer Review
• Publisher DOI: http://doi.org/10.1101/2023.02.27.530227
• Subjects: Biology, Virology
• Keywords: retrotransposon; virus-like particle; prion-like domain; Saccharomyces cerevisiae

Abstract

Retrotransposons and retroviruses shape genome evolution and can negatively impact genome function. Saccharomyces cerevisiae and its close relatives harbor several families of LTR-retrotransposons, the most abundant being Ty1 in several laboratory strains. The cytosolic foci that nucleate Ty1 virus-like particle (VLP) assembly are not well-understood. These foci, termed retrosomes or T-bodies, contain Ty1 Gag and likely Gag-Pol and the Ty1 mRNA destined for reverse transcription. Here, we report a novel intrinsically disordered N-terminal prion-like domain (PrLD) within Gag that is required for transposition. This domain contains amino-acid composition similar to known yeast prions and is sufficient to nucleate prionogenesis in an established cell-based prion reporter system. Deleting the Ty1 PrLD results in dramatic VLP assembly and retrotransposition defects but does not affect Gag protein level. Ty1 Gag chimeras in which the PrLD is replaced with other sequences, including yeast and mammalian prionogenic domains, display a range of retrotransposition phenotypes from wildtype to null. We examine these chimeras throughout the Ty1 replication cycle and find that some support retrosome formation, VLP assembly, and retrotransposition, including the yeast Sup35 prion and the mouse PrP prion. Our interchangeable Ty1 system provides a useful, genetically tractable in vivo platform for studying PrLDs, complete with a suite of robust and sensitive assays, and host modulators developed to study Ty1 retromobility. Our work invites study into the prevalence of PrLDs in additional mobile elements.