Rtr1 Is the Saccharomyces cerevisiae Homolog of a Novel Family of RNA Polymerase II-Binding Proteins

Cells must rapidly sense and respond to a wide variety of potentially cytotoxic external stressors to survive in a constantly changing environment. In a search for novel genes required for stress tolerance inSaccharomyces cerevisiae , we identified the uncharacterized open reading frame YER139C as a gene required for growth at 37°C in the presence of the heat shock mimetic formamide. YER139C encodes the closest yeast homolog of the human RPAP2 protein, recently identified as a novel RNA polymerase II (RNAPII)-associated factor. Multiple lines of evidence support a role for this gene family in transcription, prompting us to rename YER139CRTR1 (r egulator oftr anscription). The core RNAPII subunitsRPB5, RPB7 , andRPB9 were isolated as potent high-copy-number suppressors of thertr1 Δ temperature-sensitive growth phenotype, and deletion of the nonessential subunitsRPB4 andRPB9 hypersensitized cells toRTR1 overexpression. Disruption ofRTR1 resulted in mycophenolic acid sensitivity and synthetic genetic interactions with a number of genes involved in multiple phases of transcription. Consistently,rtr1 Δ cells are defective in inducible transcription from theGAL1 promoter. Rtr1 constitutively shuttles between the cytoplasm and nucleus, where it physically associates with an active RNAPII transcriptional complex. Taken together, our data reveal a role for members of the RTR1/RPAP2 family as regulators of core RNAPII function.