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Biomolecules 2015, 5(2), 1035-1062; doi:10.3390/biom5021035

Initial Events in Bacterial Transcription Initiation

1
Department of Biochemistry, University of Wisconsin-Madison, 1101 University Ave. Madison, Madison, WI 53706, USA
2
Departments of Chemistry and Biochemistry, University of Wisconsin-Madison, 1101 University Ave. Madison, Madison, WI 53706, USA
3
Department of Microbiology, The Ohio State University, 105 Biological Sciences, 484 W 12th Ave, Columbus, OH 43210, USA
4
Center for RNA Biology, The Ohio State University, 105 Biological Sciences, 484 W 12th Ave, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Deborah M. Hinton and Sivaramesh Wigneshweraraj
Received: 28 March 2015 / Accepted: 14 May 2015 / Published: 27 May 2015
(This article belongs to the Special Issue Bacterial RNA Polymerase)
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Abstract

Transcription initiation is a highly regulated step of gene expression. Here, we discuss the series of large conformational changes set in motion by initial specific binding of bacterial RNA polymerase (RNAP) to promoter DNA and their relevance for regulation. Bending and wrapping of the upstream duplex facilitates bending of the downstream duplex into the active site cleft, nucleating opening of 13 bp in the cleft. The rate-determining opening step, driven by binding free energy, forms an unstable open complex, probably with the template strand in the active site. At some promoters, this initial open complex is greatly stabilized by rearrangements of the discriminator region between the −10 element and +1 base of the nontemplate strand and of mobile in-cleft and downstream elements of RNAP. The rate of open complex formation is regulated by effects on the rapidly-reversible steps preceding DNA opening, while open complex lifetime is regulated by effects on the stabilization of the initial open complex. Intrinsic DNA opening-closing appears less regulated. This noncovalent mechanism and its regulation exhibit many analogies to mechanisms of enzyme catalysis. View Full-Text
Keywords: RNA polymerase; promoter; kinetics; mechanism; transcription regulation RNA polymerase; promoter; kinetics; mechanism; transcription regulation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ruff, E.F.; Record, M.T., Jr.; Artsimovitch, I. Initial Events in Bacterial Transcription Initiation. Biomolecules 2015, 5, 1035-1062.

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