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Eukaryotic Cell, June 2008, p. 938-948, Vol. 7, No. 6
1535-9778/08/$08.00+0     doi:10.1128/EC.00042-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Patrick A. Gibney,1 Thomas Fries,2 Susanne M. Bailer,2 and Kevin A. Morano1*

Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, Texas 77030,1 Universität des Saarlandes, Medizinische Biochemie und Molekularbiologie, Gebäude 61.4, D-66421 Homburg/Saar, Germany2

Received 1 February 2008/ Accepted 7 April 2008

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 in Saccharomyces 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 YER139C RTR1 (regulator of transcription). The core RNAPII subunits RPB5, RPB7, and RPB9 were isolated as potent high-copy-number suppressors of the rtr1{Delta} temperature-sensitive growth phenotype, and deletion of the nonessential subunits RPB4 and RPB9 hypersensitized cells to RTR1 overexpression. Disruption of RTR1 resulted in mycophenolic acid sensitivity and synthetic genetic interactions with a number of genes involved in multiple phases of transcription. Consistently, rtr1{Delta} cells are defective in inducible transcription from the GAL1 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.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, University of Texas Medical School, 6431 Fannin Street, Houston, TX 77030. Phone: (713) 500-5890. Fax: (713) 500-5499. E-mail: Kevin.A.Morano{at}uth.tmc.edu

{triangledown} Published ahead of print on 11 April 2008.

Eukaryotic Cell, June 2008, p. 938-948, Vol. 7, No. 6
1535-9778/08/$08.00+0     doi:10.1128/EC.00042-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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