RTT105 in Ty1 Retrotransposition: a Possible Role in Virus‐like Particle (VLP) Assembly

Abstract

Retrovirus‐like transposon mRNA encodes envelope and replication proteins (gag and pol), and serves as genomic material for virus‐like particles (VLPs), a cytosolic structure in which the element's genome is reverse transcribed. In Saccharomyces cerevisiae, there are several families of such retrotransposons, including the abundant Ty1 element. Previously, genome‐wide screens have identified candidate genes that mediate Ty1 mobility. One candidate, RTT105, was identified as a negative regulator of Ty1 mobility. Because RTT105 contains no conserved domains, the nature of RTT105's role in Ty1 retrotransposition remains unknown. Rtt105p localizes at Ty1 RNA and Gag foci, suggesting a role in ribonucleoprotein complexes. Here, we use RNA‐Seq analysis of isogenic WT and RTT105 knockout strains to determine changes in gene expression that may explain RTT105's regulation of Ty1. In rtt105Δ, we identified significant down regulation of signal recognition particle (SRP), a conserved chaperone that binds ribosome‐nascent chain complexes for post‐transcriptional processing. SRP aids in translocating Gag to the ER where it encapsulates Ty1 RNA in trans at presumptive VLP assembly sites. Because endogenous Ty1 mobility is maintained at low levels by the host cell, our data suggest that RTT105 may support SRP‐dependent processing of Ty1. Deletion of RTT105 may induce down regulation of SRP‐dependent processing of Ty1, thereby decreasing genome‐wide mobility of the element. This result illuminates an important step in retrotransposon processing and regulation, and suggests at least one route by which Ty1 activity is actively maintained by the cell.This research was funded by HHMI, NIH, and the Huck Institutes of the Life Sciences.