Restriction Factor Control of Ty1 Family LTR-Retrotransposons in Saccharomyces cerevisiae

Retrotransposons comprise large fractions of many genomes and numerous transposon control mechanisms have evolved to combat retrotransposon expansion. The budding yeast Saccharomyces cerevisiae contains several active retrotransposon families but maintains a remarkably compact genome, all without many of the transposon control systems used in mammals. Here, we review restriction factor control of the yeast Ty1 family of LTR-retrotransposons. Several decades of study have identified a novel mechanism that provides highly specific restriction of Ty1 using transposon-derived sequences. Recent work combining structural, biophysical, biochemical, and genetic techniques has revealed a detailed mechanism of this restriction and the determinants of specificity. Interestingly, two Ty1 subfamilies each converged on the same restriction mechanism despite following separate evolutionary histories. The protein p22/p18 is a self-encoded restriction factor that targets Ty1c and is produced from an internally initiated mRNA. Drt2 is a restriction factor that targets Ty1' and is produced from a transposon fragment endogenized by the host genome. Both interfere with the assembly of transposon virus-like particles using a shared dimerization surface, but subtle sequence divergence in this interface directs each restriction factor against its specific Ty1 subfamily. This work presents a framework to identify novel transposon control systems in other organisms.