Effectors of retrotransposon movement The retrovirus-like transposon Ty1 of Saccharomyces is an informative model for understanding how retrotransposons and retroviruses mobilize, shape the genome, and interact with host and element encoded factors. The additive nature of the retroelement replication cycle can result in massive increases in copy number if left unchecked. Host cells have countered with several defense systems, including domestication of retroelement genes that now act as restriction factors to minimize propagation. We discovered a truncated form of the Ty1 capsid protein that inhibits virus-like particle assembly and function. This self-encoded restriction factor expands the repertoire of defense proteins targeting the capsid. Our work also highlights an intriguing host-parasite strategy. Instead of inhibiting all transposon movement by domesticating the restriction gene as a distinct locus, yeast and Ty1 may have coevolved a relationship that allows high levels of transposition when copy numbers are low and progressively less transposition as copy numbers rise. Our goal is to understand the mechanism and evolution of Ty1 copy number control by a combination of genetic, genomic, cell biological, biochemical and structural approaches.
We have adopted a multidisciplinary approach, combining insights from genetics and genome sciences, cell biology, structural biology, and biochemistry to investigate a naturally produced retrotransposon protein derived from the capsid gene that disrupts the assembly and function of Ty1 virus-like particles in a dose- dependent manner. Further study will yield insight into the mechanisms used by restriction factors that inhibit virus production. Our work will also impact research on innate defense mechanisms against transposons and foreign invaders, including retroviral propagation and virus assembly.
