Melissa Wells returns to present research.

On April 7, 2010  at 11:50 a.m. in room 205/6 of Valentine Hall, we welcome
back our alum Melissa Wells who is nearing completion of a Ph.D. in
Biochemistry at the University of Virginia. 
She will also be available to speak to any undergraduates about the
University of Virginia program following her talk.


"RNA synthesis precision is regulated by
preinitiation complex turnover"


TATA-binding protein (TBP) nucleates the assembly of the
transcription preinitiation complex (PIC), and although TBP can bind promoters
with high stability in vitro, recent results establish that virtually the
entire TBP population is highly dynamic in yeast nuclei in vivo.  This dynamic behavior is surprising in light
of models which posit that a stable TBP-containing scaffold facilitates
transcription reinitiation at active promoters. 
The dynamic behavior of TBP is a consequence of the enzymatic activity
of the essential Snf2/Swi2 ATPase Mot1, suggesting that ensuring a highly mobile
TBP population is critical for transcriptional regulation on a global
scale.  High-resolution tiling arrays
were used to define how perturbed TBP dynamics impact the precision of RNA
synthesis in Saccharomyces cerevisiae. 
We find that Mot1 plays a broad role in establishing the fidelity and
efficiency of RNA synthesis: in mot1-42 cells, RNA length changes were observed
for 713 genes.  Loss of Mot1 led to both
aberrant transcription initiation and termination events, with most changes
involving stochastic premature termination. Genetic and genomic analyses
support the conclusion that these effects on RNA length are mechanistically
tied to dynamic TBP occupancies at certain types of promoters.  These results suggest a new model whereby
dynamic disassembly of the PIC can influence productive RNA synthesis.