The Ty1 Retrotransposon Restriction Factor p22 Targets Gag

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The presence of transposable elements in the eukaryotic genome threatens genomic stability and normal gene function, thus various defense mechanisms exist to silence element expression and target integration to benign locations in the genome. Even though the budding yeast Saccharomyces lacks many of the defense systems present in other eukaryotes, including RNAi, DNA methylation, and APOBEC3 proteins, they maintain low numbers of mobile elements in their genome. In the case of the Saccharomyces retrotransposon Ty1, a system called copy number control (CNC) helps determine the number of elements in the genome. Recently, we demonstrated that the mechanism of CNC relies on a trans-acting protein inhibitor of Ty1 expressed from the element itself. This protein inhibitor, called p22, impacts the replication of Ty1 as its copy number increases. To identify a molecular target of p22, mutagenized Ty1 was subjected to a forward genetic screen for CNC-resistance. Mutations in specific domains of Gag, including the UBN2 Gag motif and a novel region we have named the CNCR domain, confer CNCR by preventing the incorporation of p22 into assembling virus-like particles (VLPs), which restores maturation and completion of the Ty1 life cycle. The mechanism of Ty1 inhibition by p22 is conceptually similar to Gag-like restriction factors in mammals since they inhibit normal particle function. In particular, resistance to p22 and the enJS56A1 restriction factor of sheep involves exclusion of the restriction factor during particle assembly, although Ty1 CNCR achieves this in a way that is distinct from the Jaagsiekte retrovirus escape mutants. Our work introduces an intriguing variation on resistance mechanisms to retroviral restriction factors.

Vyšlo v časopise: The Ty1 Retrotransposon Restriction Factor p22 Targets Gag. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005571
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005571

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