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J. Biol. Chem., Vol. 277, Issue 22, 19488-19497, May 31, 2002
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§¶
From the 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.
Department of Molecular Genetics and
§ Program in Molecular, Cellular, and Developmental Biology,
Ohio State University, Columbus, Ohio 43210
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