Ty1 escapes restriction by the self-encoded factor p22 through mutations in capsid.

Ty1 is a long terminal repeat (LTR) retrotransposon belonging to the Ty1/copia family and is present in up to 32 full-length copies in Saccharomyces. Like retroviruses, Ty1 contains GAG and POL genes, LTRs, and replicates via an RNA intermediate within a virus-like particle (VLP). Although Ty1 retrotransposition is not infectious, uncontrolled replication can lead to detrimental effects on the host genome, including insertional mutagenesis and chromosomal rearrangements. Ty1 copy number control (CNC) limits replication and is mediated through a self-encoded protein called p22. p22 is translated from a subgenomic Ty1 RNA and encodes an amino-truncated version of the Gag protein. We highlight a recent study identifying Ty1 Gag, which comprises the VLP capsid and provides nucleic acid chaperone functions, as a direct target of p22-mediated inhibition. CNC-resistant (CNC(R)) mutations map within predicted helical domains of Gag, including those in the Ty1/copia pfam domain Retrotran_gag_2 (formerly UBN2) and a central region we refer to as the CNC(R) domain. CNC(R) Gag forms VLPs that exclude p22, thus restoring Ty1 replication. We discuss possible mechanisms for p22 inclusion in Ty1 VLPs and compare Ty1 CNC with retroviral restriction factors targeting capsid (CA).