Abstract
RNA polymerase is among the most highly regulated enzymes in nature, and serves as a central integrator of diverse circuits that monitor and control a cell’s metabolic state, developmental program, and extracellular environment. To achieve this extent of regulation, evolution has imbued the RNA polymerase with multiple, intricate, and interconnected modes of regulation that control transcriptional initiation, elongation, and termination. These regulatory modes include control of the RNA polymerase catalytic center, which depends on conformational alternation of the polymorphous trigger loop between an unfolded state that allows substrate NTP binding and a helical hairpin that contacts the NTP and is required for efficient nucleotide addition. Folding of the trigger loop is modulated indirectly by regulatory proteins that contact the enzyme surface and by nascent RNA secondary structures that form in the RNA exit channel. In some bacteria, including E. coli, folding is modulated directly by a large domain (188 aa in E. coli) that is inserted directly into the trigger loop and that, remarkably, serves as a mutational target to allow reprogramming of RNA polymerase to different growth environments by small alterations that arise during adaptive evolution. In vivo control of transcript elongation frequently involves promoter-proximal pausing by RNA polymerase, which provides a platform for recruitment of elongation regulators in synergy with ribosome binding to nascent mRNAs.
About the speaker
Prof Robert Landick received his PhD from the University of Michigan in 1983. He started his independent academic career at Washington University at St Louis and rose to the rank of the full Professor of Biology. In 1996, he moved to the University of Wisconsin-Madison, at which he is currently the Charles Yanofsky Professor of Biochemistry & Bacteriology at the Department of Biochemistry.
Prof Landick is an expert on structure and function of RNA polymerase, one of the key cellular machinery of gene expression. His interest spans multiple disciplines from single-molecule experiments to genome-scale mechanisms of gene regulation. His work has defined an elemental mechanism of transcriptional pausing for both bacterial and human RNA polymerases, established how paused states can be prolonged or shortened by regulators, and identified roles for transcriptional pausing in fundamental mechanisms of gene regulation and in RNA folding. He is a fellow of the American Association for the Advancement of Science and fellow of the American Academy of Microbiology. He currently leads a microbial engineering research program in the Great Lakes Bioenergy Center.
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