Transcription factors modulate RNA polymerase conformational equilibrium.

Bacterial Proteins; Escherichia coli Proteins; NusG protein, E coli; Peptide Elongation Factors; Transcription Factors; Transcriptional Elongation Factors; nusA protein, E coli; EC 2.7.7.6 (DNA-Directed RNA Polymerases); Bacterial Proteins/metabolism; DNA-Directed RNA Polymerases/metabolism; Escherichia coli/genetics/metabolism; Escherichia coli Proteins/metabolism; Nucleic Acid Conformation; Peptide Elongation Factors/metabolism; Transcription Factors/metabolism; Transcription, Genetic; Transcriptional Elongation Factors/metabolism

Abstract :

[en] RNA polymerase (RNAP) frequently pauses during the transcription of DNA to RNA to regulate gene expression. Transcription factors NusA and NusG modulate pausing, have opposing roles, but can bind RNAP simultaneously. Here we report cryo-EM reconstructions of Escherichia coli RNAP bound to NusG, or NusA, or both. RNAP conformational changes, referred to as swivelling, correlate with transcriptional pausing. NusA facilitates RNAP swivelling to further increase pausing, while NusG counteracts this role. Their structural effects are consistent with biochemical results on two categories of transcriptional pauses. In addition, the structures suggest a cooperative mechanism of NusA and NusG during Rho-mediated transcription termination. Our results provide a structural rationale for the stochastic nature of pausing and termination and how NusA and NusG can modulate it.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Zhu, Chengjin; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Guo, Xieyang; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France. ; GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK.

Dumas, Philippe; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Takacs, Maria ; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Abdelkareem, Mo'men; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Vanden Broeck, Arnaud ; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Saint-André, Charlotte; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Papai, Gabor; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Crucifix, Corinne; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France.

Ortiz, Julio ; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. ; Université de Strasbourg, 67404, Illkirch, France. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France. ; Forschungszentrum Jülich, Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons, Jülich, Germany.

Weixlbaumer, Albert ; Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404, Illkirch, France. albert.weixlbaumer@igbmc.fr. ; Université de Strasbourg, 67404, Illkirch, France. albert.weixlbaumer@igbmc.fr. ; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. albert.weixlbaumer@igbmc.fr. ; Institut National de la Santé et de la Recherche Médicale, U1258, 67404, Illkirch, France. albert.weixlbaumer@igbmc.fr.

Language :

English

Title :

Transcription factors modulate RNA polymerase conformational equilibrium.

Publication date :

22 March 2022

Journal title :

Nature Communications

eISSN :

2041-1723

Publisher :

Nature Publishing Group, London, Gb

Volume :

Issue :

Pages :

1546

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 01 October 2024

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