Ribosome abundance is directly proportional to cell growth and proliferation rates. Nucleolar size and ribosomal RNA (rRNA) synthetic activity have been used as indicators of cell transformation for more than 100 years. The overall goal of our lab is to characterize the molecular mechanisms that control transcription of rRNA by RNA polymerase I (Pol I) and subsequent rRNA processing events.
Our current interests include:
We use a large variety of strategies to investigate these questions including: genetic analyses (screens, in vivo rRNA synthesis assays, ChIP), biophysical analyses (mass spectrometry, in collaboration with Dr. Matthew Renfrow; UAB), biochemical analyses (in vitro enzymology of Pol I) and electron microscopy (in collaboration with Dr. Ann Beyer, University of Virginia). One example of our implementation of diverse techniques to address a fundamentally important question is shown in the accompanying figure. We used a genetic screen to identify a mutation in Pol I (A135 subunit) that rendered cells sensitive to the transcription elongation inhibitor 6-azauracil. We then purified the mutant enzyme and demonstrated its transcription elongation rate was significantly slower than wild-type. Ultimately, we used that mutant strain to demonstrate, for the first time, that transcription elongation by Pol I is functionally coupled to processing/folding of rRNA.
Our long-term goal is to fully characterize factors that regulate initiation and elongation steps in Pol I transcription. Without understanding the robust mechanisms that control and optimize transcription initiation and elongation by Pol I, the long known role for ribosome synthesis in cell transformation cannot be defined or controlled.
Dr. Schneider was raised in the suburbs of Atlanta, GA. He obtained his B.S. in microbiology and genetics from the University of Georgia in 1998. As an undergraduate he studied molecular biology of bacteriophage. As a graduate student at the University of Wisconsin (1998 - 2003), he moved up the tree of life to study the effect of small molecule regulators on transcription in bacteria. For his postdoctoral studies at the University of California, Irvine (2003 - 2007), he inched further up the tree of life to study the molecular mechanisms by which RNA polymerase I is regulated in eukaryotic cells. His work continues to focus on studies in model eukaryotic cells (yeast). Dr. Schneider joined the faculty as an Assistant Professor at UAB in 2007.