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A more recent version of this article appeared on May 24, 2002
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M201878200v1
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Papers In Press, published online ahead of print March 21, 2002
J. Biol. Chem, 10.1074/jbc.M201878200
Submitted on February 25, 2002
Revised on March 21, 2002
Accepted on March 21, 2002

The C-terminal domain (CTD) 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. Howard, Yelena V. Budovskaya, Ya-Wen Chang, and Paul K. Herman

Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210

Corresponding Author: herman.81{at}osu.edu

The S. 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, or 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.


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