The Mediator co-activator complex regulates Ty1 retromobility by controlling the balance between Ty1i and Ty1 promoters

Abstract

4The Ty1 retrotransposons present in the genome of Saccharomyces cerevisiae belong to the large class 3 5 of mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of 3 6 most eukaryotic genomes. The retromobility of Ty1 is regulated by numerous host factors, including 3 7 several subunits of the Mediator transcriptional co-activator complex. In spite of its known function in 3 8 the nucleus, previous studies have implicated Mediator in the regulation of post-translational steps in 3 9 Ty1 retromobility. To resolve this paradox, we systematically examined the effects of deleting non-4 0 essential Mediator subunits on the frequency of Ty1 retromobility and levels of retromobility 4 1 intermediates. Our findings reveal that loss of distinct Mediator subunits alters Ty1 retromobility 4 2 positively or negatively over a >10,000-fold range by regulating the ratio of an internal transcript, Ty1i, 4 3 to the genomic Ty1 transcript. Ty1i RNA encodes a dominant negative inhibitor of Ty1 retromobility 4 4 that blocks virus-like particle maturation and cDNA synthesis. These results resolve the conundrum of 4 5