description): The phosphorylation state of the largest subunit of RNA polymerase II determines its ability to be recruited into a preinitiation complex or carry out efficient RNA chain elongation. Further, the C-terminal heptapeptide repeat domain (CTD) that is the target for phosphorylation is essential for several additional steps in mRNA biogenesis, including mRNA capping, splicing, and 3' end processing. Thus it is likely that CTD phosphorylation regulates all of these processes in the cell. Understanding the mechanisms that govern CTD phosphorylation and dephosphorylation is critical to learning how transcription is coordinated with other steps in nuclear RNA metabolism. Numerous protein kinases capable of phosphorylating the CTD on different sites are known, but CTD-specific phosphatases have not been described until recently, with the purification and cloning of a yeast serine/threonine phosphatase subunit capable of this reaction, and the discovery of a mammalian homologue. The phosphatase subunit encoded by the essential FCP1 gene is not sufficient for CTD dephosphorylation activity in vitro, and an unknown positive cofactor (FcpX) has been implicated. Further, the phosphatase activity is inhibited by the HIV Tat protein, which is known to stimulate elongation by the hyperphosphorylated form of RNA polymerase II.
The aims of this research are to: (1) Isolate and characterize the cofactor FcpX; (2) Carry out a structure-function analysis of FCP1 using yeast genetics and biochemistry; and (3) determine the role(s) of Fcp1 in the cell using genetic suppressor analysis combined with biochemistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060498-04
Application #
6603376
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Tompkins, Laurie
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2003
Total Cost
$265,034
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704