|Address:||Kaul Human Genetics Building
720 20th Street South
Birmingham, AL 35294-0024
Control of Gene Expression: molecular mechanisms that regulate RNA polymerase I transcription initiation and elongation.
Synthesis of ribosomes is a sophisticated and tightly controlled process in all living cells. Transcription of ribosomal RNA (rRNA) by RNA polymerase I can account for more than 60% of the total transcription in a growing cell. Given the energetic commitment that cells must make to build ribosomes, it is obvious that efficient control of this process is essential. The molecular mechanisms that control the synthesis of rRNA are the focus of my research group.
The research in my lab addresses three general questions:
(1) How is transcription initiation by RNA polymerase I regulated?
(2) What cellular factors affect the efficiency of RNA polymerase I transcription elongation?
(3) How do changes in transcription elongation efficiency affect rRNA processing and ribosome assembly?
To address these questions we perform a variety of biochemical and genetic experiments using the model eukaryote Saccharomyces cerevisiae. The yeast system enables us to do advanced genetic analyses and detailed biochemical experiments to fully address the questions posed above.
These studies are, of course, important from a basic biological standpoint. Additionally, the continued characterization of mechanisms that control rRNA synthesis is important for health related issues. Since the majority of a growing or proliferating cell’s energy is devoted to ribosome synthesis one would expect a strong correlation between the transcription rate of rRNA by RNA polymerase I and uncontrolled cell growth and proliferation (ie. cancer). Indeed, rRNA synthesis rate and nucleolar size have long been used as indicators of cell transformation. Thus, a molecular understanding of the processes that regulate RNA polymerase I activity will potentially have long term effects on the ability to control or eliminate cancer cell growth.