Meiotic Cells Counteract Programmed Retrotransposon Activation Via RNA-Binding Translational Repressor Assemblies

While retrotransposons must activate in developing gametes in order to survive and propagate, how a retrotransposon selectively activates in the context of meiosis is unclear. These mobile genetic elements can promote evolutionary innovations, but their unchecked proliferation is catastrophic for their host. Consequently, organisms have developed elegant mechanisms to counteract retrotransposon proliferation. In this manuscript, we demonstrate that both transcriptional activation of Ty3/Gypsy retrotransposons and host defense are controlled by master meiotic regulators. We show that Ty3 retrotransposons in budding yeast co-opt binding sites of the essential meiotic transcription factor Ndt80 upstream of the integration site, thereby tightly linking their transcriptional activation to meiotic progression. Our results raise the question of how yeast protects the genomes of its developing gametes from retrotransposon proliferation during meiosis. We elucidate how yeast cells thwart the Ty3/Gypsy retrotransposition life cycle by blocking translation of the retrotransposon mRNA using amyloid-like assemblies of the RNA-binding protein Rim4. In mammals, Gypsy elements have lost retrotransposition capacity. Building from our findings in yeast, we show that developing gametes in mammals also utilize essential meiotic transcription factors and assembly-forming RNA-binding proteins to regulate Gypsy-derived genes. Our findings inform how novel genes that are evolving from retrotransposons can build upon existing regulatory networks during domestication.