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Originally published In Press as doi:10.1074/jbc.M201878200 on March 21, 2002

J. Biol. Chem., Vol. 277, Issue 22, 19488-19497, May 31, 2002
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The C-terminal Domain of the Largest Subunit of RNA Polymerase II Is Required for Stationary Phase Entry and Functionally Interacts with the Ras/PKA Signaling Pathway*

Susie C. HowardDagger , Yelena V. BudovskayaDagger , Ya-Wen Chang§, and Paul K. HermanDagger §

From the Dagger  Department of Molecular Genetics and § Program in Molecular, Cellular, and Developmental Biology, Ohio State University, Columbus, Ohio 43210

The Saccharomyces cerevisiae Ras proteins control cell growth by regulating the activity of the cAMP-dependent protein kinase (PKA). In this study, a genetic approach was used to identify cellular processes that were regulated by Ras/PKA signaling activity. Interestingly, we found that mutations affecting the C-terminal domain (CTD), of Rpb1p, the largest subunit of RNA polymerase II, were very sensitive to changes in Ras signaling activity. The Rpb1p CTD is a highly conserved, repetitive structure that is a key site of control during the production of a mature mRNA molecule. We found that mutations compromising the CTD were synthetically lethal with alterations that led to elevated levels of Ras/PKA signaling. Altogether, the data suggested that Ras/PKA activity was negatively regulating a protein that functioned in concert with the CTD during RNA pol II transcription. Consistent with this prediction, we found that elevated levels of Ras signaling caused growth and transcription defects that were very similar to those observed in mutants encoding an Rpb1p with a truncated CTD. In all, these data suggested that S. cerevisiae growth control and RNA pol II transcription might be coupled by using the Ras pathway to regulate CTD function.


* This work was supported by grants from the Ohio Cancer Research Associates and the National Science Foundation (to P. K. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Molecular Genetics, Rm. 984, Ohio State University, 484 West Twelfth Ave., Columbus, OH 43210. Tel.: 614-688-5581; Fax: 614-292-4466; E-mail: herman.81@osu.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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