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MOLECULAR ANALYSIS OF RNA POLYMERASE II 
Jeffry L. Corden, Ph.D., Associate Investigator 
Research in Dr. Corden's laboratory continues to 
focus on the unusual repeated sequence at the car- 
boxyl terminus of the largest subunit of RNA poly- 
merase II. This carboxyl-terminal domain (CTD) 
consists of tandem repeats of a seven-amino acid 
consensus sequence, TyrSerProThrSerProSer. This 
sequence is repeated from 17 to 52 times in differ- 
ent organisms. The CTD plays an essential role in the 
transcription process, but the mechanism by which 
it acts is unknown. Studies ongoing in Dr. Corden's 
laboratory are designed to elucidate the structure 
and function of this domain, using yeast and mouse 
as model systems. 
The unusual sequence of the CTD suggests that it 
adopts a repetitive turn structure. Previous work 
from Dr. Corden's laboratory demonstrated that 
phosphorylation of serine residues in positions two 
and five of each repeat results in a conformational 
change that stiffens or unfolds the CTD. To address 
the molecular basis of this change, the structure of 
the phosphorylated and unphosphorylated CTDs are 
being compared. Nuclear magnetic resonance 
(NMR) spectra of model CTD peptides suggest the 
presence of two separate |5-turn structures in each 
repeat of the unphosphorylated CTD. How these 
turns are linked in the full-length CTD is now under 
investigation. 
In addition, the role of serine residues in main- 
taining the structure of the CTD is being addressed 
by studies of model peptides in which the phos- 
phorylatable serines have been changed to alanine 
or glutamate. These CTD repeat variants are identi- 
cal to the mutant CTDs that have been genetically 
tested in yeast cells. 
To investigate the function of the CTD, the labora- 
tory has initiated a comprehensive genetic analysis 
of the yeast CTD. The purposes of this analysis are 1 ) 
to determine which CTD sequences are essential for 
cell viability, 2) to determine the basis of the slow- 
growth phenotype of some CTD mutations, and 3) 
to isolate suppressors of CTD mutants and thereby 
identify molecules that interact with this domain. 
GENETICS 175 
