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David Price, PhD


Office: 3130 MERF
Office Phone: 319-335-7910

Lab: 3120 MERF

Lab Website: https://price.lab.uiowa.edu/

Discovering connections between transcription elongation and RNA processing, HIV replication, and cancer

Understanding how mRNA levels are controlled in eukaryotes requires dissection of the intricate pathway responsible for the synthesis and processing of mRNA. Previously, we obtained evidence for a general eukaryotic transcription regulatory process that controls the number of polymerase molecules that are able to produce full-length mRNAs. We discovered P-TEFb, a cyclin dependent kinase that plays a key role in this elongation control process. The kinase activity of P-TEFb is required for eukaryotic gene expression and recent results indicate that cells carefully regulate P-TEFb through an unusual association with a 7SK snRNP containing HEXIM1, MEPCE, and LARP7. We are currently engaged in projects to uncover the mechanism of P-TEFb function and how it is regulated. The AIDS virus, HIV, encodes a protein, Tat, that enables the virus to take over the control of P-TEFb. We are studying Tat-transactivation and are examining the mechanism of action of drugs that target this critical step in the HIV life cycle. Our basic research on factors that influence elongation by RNA polymerase II also uncovered the first RNA polymerase II termination factor, TTF2. Current results indicate that this factor plays a role in mitotic repression of transcription elongation and, perhaps, DNA repair. We developed new in vitro assays to study the mechanistic details of the interaction of RNA processing machinery with the transcription complex and have shown that most RNA processing events are functionally coupled to transcription. We have begun to use chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to map the location of RNA polymerase II and elongation factors across the human genome (see figure). This new technique opens up new avenues of discovery previously not possible. Overall, we use biochemical, molecular and cellular techniques to advance our understanding of the control of RNA polymerase II elongation and how that process influences RNA processing, HIV replication and cancer growth.

PubMed link

Department/Program Affiliations:
Molecular Medicine