RTF1 was originally identified in a search for suppressors of a
TBP altered specificity mutant. To elucidate the function of Rtf1, a
synthetic lethal screen with an rtf1 null allele was performed.
The screen identified mutations in nine genes. The cloning of six of
the genes showed that they define two classes. SWI4 and
SWI6 encode activators of various cell-cycle regulated
promoters, while SRB5, CTK1, FCP1, and
POB3 have more global roles in transcription. Specifically,
SRB5, CTK1, and FCP1 directly affect the
phosphorylation state of the C-terminal domain (CTD) of RNA polymerase
II. The isolation of mutations in these genes argues that Rtf1
function is essential when CTD phosphorylation is abnormal. Because
the extent of CTD phosphorylation correlates strongly with progression
from transcription initiation to elongation, our results also suggest
that Rtf1 may be important for this transition, particularly in the
context of chromatin. Interestingly, we uncovered a POB3
mutation in our screen. Pob3 shares similarity with HMG1-like proteins
and forms a complex with Cdc68/Spt16. The human counterparts of Pob3
and Cdc68/Spt16 form a nucleosome-specific transcription elongation
factor. A role for Rtf1 in elongation is further supported by
interactions between RTF1 and genes encoding several known
elongation factors. In addition, rtfl null mutations confer
sensitivity to 6-azauracil and mycophenolic acid, phenotypes
associated with defects in transcription elongation.
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