CHAPTER 5: Rho Termination Factor: One Ring to Bind Them All
Published:23 Nov 2021
N. D. Sunday, D. Svetlov, and I. Artsimovitch, in RNA Polymerases as Molecular Motors: On the Road, ed. R. Landick, T. Strick, and J. Wang, The Royal Society of Chemistry, 2nd edn, 2021, pp. 100-131.
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The hexameric, ring-shaped bacterial termination factor Rho performs many functions: inducing termination at the end of genes, silencing transcriptional noise, reducing translational stress, and preventing replication–transcription collisions. Genome-wide studies implicate Rho in genome stability and adaptation to changing environments and demonstrate that its numerous cellular targets lack an easily recognizable consensus sequence. Results from decades of structural and biochemical studies were indicative of a steric model of action in which an open-ring Rho self-loads onto nascent RNA; subsequent closure of the ring transforms Rho into a powerful ATPase that translocates along the nascent RNA, unwinding nucleic-acid duplexes and releasing transcribing RNA polymerase. Recent work provides evidence for an alternative, and physiologically more consequential, allosteric model, in which Rho is recruited to RNA polymerase and transforms active elongation complexes into moribund pre-termination complexes from which RNA is subsequently released. This transformation occurs through an intricate pathway of multiple intermediates, involving Rho contacts with RNA polymerase subunits and the general transcription factors N-utilizing substance A (NusA) and N-utilizing substance G (NusG), indicating the presence of numerous regulatory routes and checkpoints. In this chapter, we summarize the well-established structural and regulatory features of Rho, interpret them in the context of significant recent findings, and discuss the major unresolved aspects of the Rho mechanism and its cellular roles.