Robert C. Landick
Department of Bacteriology
University of Wisconsin
1550 Linden Dr.
Madison, WI 53706
1987 Searle Scholar
At the heart of most genetic regulatory mechanisms lies RNA polymerase. This remarkable molecular machine responds to the metabolic, physical, and developmental state of living organisms not simply via activators and repressors that control its access to promoters, but also because intrinsic signals and trans-acting proteins or RNAs influence the rate and efficiency with which it completes RNA chains. Despite the important role of elongation control mechanisms in gene expression, we lack a detailed understanding of how RNA polymerase responds to the intrinsic pause and termination signals that underlie them. E. coli is an ideal model system to study these fundamental mechanisms. Here, we dissect recognition of pause and termination signals from the his and trp operon attenuators to probe structural features of the transcription complex that control RNA chain extension. Recognition depends on discrete interactions between different parts of these signals, (e.g., nascent RNA structures and downstream DNA sequences) with RNA polymerase. These interactions convert a rapidly elongating polymerase to paused or termination conformations by inducing an inchworm-like movement of the enzyme on the RNA and DNA chains. Using molecular genetics, protein crosslinking, protein footprinting, and structural probes of the RNA and DNA, we hope to identify the responsive parts of the enzyme and understand the structural basis of these conformational changes.
Our laboratory pursues parallel studies of human RNA polymerase II, using the effect of the HIV Tat protein on chain elongation as a model. To develop new tools for understanding both the bacterial and human systems in detail, the lab collaborates with biophysicists to analyze transcription by single RNA polymerase molecules by video microscopy and to obtain ~15 Å, 3D structures of active transcription complexes by electron crystallography.
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