Ty3 Retrotransposon Hijacks Mating Yeast RNA Processing Bodies to Infect New Genomes

Retrotransposition of the budding yeast long terminal repeat retrotransposon Ty3 is activated during mating. In this study, proteins that associate with Ty3 Gag3 capsid protein during virus-like particle (VLP) assembly were identified by mass spectrometry and screened for roles in mating-stimulated retrotransposition. Components of RNA processing bodies including DEAD box helicases Dhh1/DDX6 and Ded1/DDX3, Sm-like protein Lsm1, decapping protein Dcp2, and 5’ to 3’ exonuclease Xrn1 were among the proteins identified. These proteins associated with Ty3 proteins and RNA, and were required for formation of Ty3 VLP retrosome assembly factories and for retrotransposition. Specifically, Dhh1/DDX6 was required for normal levels of Ty3 genomic RNA, and Lsm1 and Xrn1 were required for association of Ty3 protein and RNA into retrosomes. This role for components of RNA processing bodies in promoting VLP assembly and retrotransposition during mating in a yeast that lacks RNA interference, contrasts with roles proposed for orthologous components in animal germ cell ribonucleoprotein granules in turnover and epigenetic suppression of retrotransposon RNAs.
Author Summary Cells undergoing changes in gene expression programs such as nutritional deprivation and other stresses exhibit formation of ribonucleoprotein (RNP) complexes. In Saccharomyces cerevisiae, the majority of investigations to date involve analysis of P-body (PB) and stress-granule RNP formation following nutritional stress. Few studies have investigated RNP formation induced by the mating-MAP-kinase pathway. In this study, we examined how this process influences genome stability via control of retrotransposon activation. During the mating response, expression of the retrotransposon Ty3 is induced and Ty3 virus-like particles form in RNP clusters called retrosomes. We show that mating retrosomes contain PB components that are essential for Ty3 expression, re-localization of Ty3 RNA and protein from polysomes into foci, and retrotransposition. In animal germ cell lineages, PB components are found in perinuclear complexes with RNA interference suppressors of retrotransposition. We speculate that when RNA interference is relaxed and retrotransposition is observed, some members of these complexes play positive roles as we observe in budding yeast.