Mechanism for the Regulated Control of Bacterial Transcription Termination by a Universal Adaptor Protein

• Published in: Molecular cell 2018-09, Vol.71 (6), p.911-922.e4
• Main Authors: Lawson, Michael R., Ma, Wen, Bellecourt, Michael J., Artsimovitch, Irina, Martin, Andreas, Landick, Robert, Schulten, Klaus, Berger, James M.
• Format: Article
• Language: English
• Subjects: ATPase; Bacterial Proteins; Chromosomal Proteins, Non-Histone - physiology; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; Escherichia coli Proteins - physiology; Models, Molecular; NusG; Peptide Elongation Factors - metabolism; Peptide Elongation Factors - physiology; Protein Conformation; Rho; Rho Factor - metabolism; Rho Factor - physiology; RNA, Bacterial; Spt5; termination; transcription; Transcription Factors - metabolism; Transcription Factors - physiology; Transcription Termination, Genetic - physiology; Transcription, Genetic - genetics; Transcription, Genetic - physiology; Transcriptional Elongation Factors - physiology; translation
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2018.07.014

NusG/Spt5 proteins are the only transcription factors utilized by all cellular organisms. In enterobacteria, NusG antagonizes the transcription termination activity of Rho, a hexameric helicase, during the synthesis of ribosomal and actively translated mRNAs. Paradoxically, NusG helps Rho act on untranslated transcripts, including non-canonical antisense RNAs and those arising from translational stress; how NusG fulfills these disparate functions is unknown. Here, we demonstrate that NusG activates Rho by assisting helicase isomerization from an open-ring, RNA-loading state to a closed-ring, catalytically active translocase. A crystal structure of closed-ring Rho in complex with NusG reveals the physical basis for this activation and further explains how Rho is excluded from translationally competent RNAs. This study demonstrates how a universally conserved transcription factor acts to modulate the activity of a ring-shaped ATPase motor and establishes how the innate sequence bias of a termination factor can be modulated to silence pervasive, aberrant transcription. [Display omitted] •NusG triggers an allosteric relay in Rho to promote activity on nonideal substrates•Rho can be reprogrammed to bypass NusG for transcription termination•NusE directly competes with Rho for binding to NusG to promote antitermination•NusG paralogs lack Rho-binding determinants, explaining functional specificity Lawson et al. show that NusG, a member of a universally conserved transcription factor family, helps isomerize the Rho transcription termination factor from an open-ring loading state to an active, closed-ring conformation. This action overrides the innate sequence bias of Rho to terminate aberrant transcriptional events emanating from translational stress.