Structures of the RNA polymerase-σ54 reveal new and conserved regulatory strategies
Keeping gene transcription in check
Transcription of all genes is carried out by RNA polymerase (RNAP). The enzyme is thus a pivotal regulation point for many cell and developmental processes. In bacteria, sigma factors play a vital role in transcription regulation, with σ54 being critical for transcription of many stress response genes. Yang et al. determined the x-ray crystal structure of RNAP bound to σ54, as well as promoter DNA. In the initial inhibited state of the RNAP-σ54 complex, the σ54 blocks the template DNA from entering the RNAP active site and the downstream DNA channel.
Science, this issue p. 882
Abstract
Transcription by RNA polymerase (RNAP) in bacteria requires specific promoter recognition by σ factors. The major variant σ factor (σ54) initially forms a transcriptionally silent complex requiring specialized adenosine triphosphate–dependent activators for initiation. Our crystal structure of the 450-kilodalton RNAP-σ54 holoenzyme at 3.8 angstroms reveals molecular details of σ54 and its interactions with RNAP. The structure explains how σ54 targets different regions in RNAP to exert its inhibitory function. Although σ54 and the major σ factor, σ70, have similar functional domains and contact similar regions of RNAP, unanticipated differences are observed in their domain arrangement and interactions with RNAP, explaining their distinct properties. Furthermore, we observe evolutionarily conserved regulatory hotspots in RNAPs that can be targeted by a diverse range of mechanisms to fine tune transcription.
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Supplementary Material
Summary
Materials and Methods
Figs. S1 to S5
Tables S1
Resources
File (aab1478-yang-sm.pdf)
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Information & Authors
Information
Published In
Science
Volume 349 | Issue 6250
21 August 2015
21 August 2015
Copyright
Copyright © 2015, American Association for the Advancement of Science.
Submission history
Received: 20 March 2015
Accepted: 15 July 2015
Published in print: 21 August 2015
Acknowledgments
We thank M. Michael and D. Bose for their earlier contributions to this project; A. Forster, J. Liu, and beamline scientists at the Diamond Light Source for their help with data collection; and members of X.Z.’s and M.B.’s labs for helpful discussion. We thank D. Wigley, R. Dixon, R. Weinzierl, C. Fernández-Tornero, and R. Wigneshweraraj for critically reading the manuscript. Y.Y. was funded by the Chinese National Science Foundation and the China Scholarship Council. The majority of this work was funded by the UK Biotechnology and Biological Sciences Research Council to X.Z. and M.B. K.S.M. is supported by NIH grant GM087350. Y.-P.W. is funded by 973 National Key Basic Research Programme (2015CB755700) in China. J.T.W. and R.L.G. were supported by NIH grant R37 GM37048 (to R.L.G.). The atomic coordinate has been deposited in the Protein Data Bank with accession code 5BYH.
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