Abstract
RNA in all cellular organisms is synthesized by a complex molecular machine, the DNA-dependent RNA polymerase (RNAP). In its simplest bacterial form, the enzyme comprises four subunits with a total molecular mass of ~400 kDa. Electron microscopy, combined with the analysis of two-dimensional crystals, provided the only structural information on cellular RNAPs (low-resolution) until 1999 when X-ray crystallograpy became possible. Since then, X-ray crystallographic analyses of bacterial RNAPs and transcription complexes have provided ever more detailed mechanistic insights into RNAP function and regulation. A detailed structural and functional understanding of the entire transcription cycle is essential to explain the fundamental control of gene expression. Advances in this understanding are stuck on the difficulty of visualizing transient intermediates that underlie key transitions between stable states of the transcription cycle, and the difficulty of visualizing complex macromolecular assemblies involved in regulation, structural problems where X-ray crystallography has severe limitations. Due to recent advances, cryo-electron microscopy (cryo-EM) now offers a route to structural and mechanistic characterization of these intermediates and large assemblies.
About the speaker
Prof Seth Darst obtained his BS in Chemical Engineering from University of Colorado, Boulder in 1982 and PhD in Chemical Engineering from Stanford University in 1987. He stayed in Stanford as the American Cancer Society Postdoctoral Fellow and joined The Rockefeller University as an Assistant Professor in 1992. He is currently the Jack Fishman Professor and Head of Laboratory of Molecular Biophysics at The Rockefeller University.
Prof Darst’s research explores the mechanism and regulation of transcription by determining three-dimensional structures of RNA polymerase and associated proteins. The RNA polymerase is conserved from bacteria to humans, making the simpler bacterial version an excellent model for understanding how transcription and, by extension, gene expression are controlled.
Prof Darst was named a Pew Scholar in the Biomedical Sciences in 1995 and a Career Scientist of the Irma T. Hirschl Charitable Trust in 1994. He was also elected a fellow of the American Academy of Microbiology and a member of the US National Academy of Sciences.
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