Ubiquitous transcription factors display structural plasticity and diverse functions

Abstract

Numerous accessory factors modulate RNA polymerase response to regulatory signals and cellular cues and establish communications with co-transcriptional RNA processing. Transcription regulators are astonishingly diverse, with similar mechanisms arising via convergent evolution. NusG/Spt5 elongation factors comprise the only universally conserved and ancient family of regulators. They bind to the conserved clamp helices domain of RNA polymerase, which also interacts with non-homologous initiation factors in all domains of life, and reach across the DNA channel to form processivity clamps that enable uninterrupted RNA chain synthesis. In addition to this ubiquitous function, NusG homologs exert diverse, and sometimes opposite, effects on gene expression by competing with each other and other regulators for binding to the clamp helices and by recruiting auxiliary factors that facilitate termination, antitermination, splicing, translation, etc. This surprisingly diverse range of activities and the underlying unprecedented structural changes make studies of these “transformer” proteins both challenging and rewarding.

Expression of the Yersinia enterocolitica O:3 LPS O-antigen and outer core gene clusters is RfaH-dependent

“…Overproduction of RfaH, however, increased the production of capsular polysaccharide in E. coli K4 (Cimini et al, 2013). Furthermore, in E. coli, RfaH and NusG are known to interact with the ribosomal protein S10 coupling transcription with translation (Burmann et al, 2010(Burmann et al, , 2012NandyMazumdar & Artsimovitch, 2015). RfaH was also implicated in regulation on the post-transcriptional level by affecting the function of small RNA MicA (Moores et al, 2014).…”

Bacterial Transcription as a Target for Antibacterial Drug Development

“…NusG SP factors. While essentially all microbes contain a gene encoding a NusG transcription elongation factor, many also contain paralogous NusG-like proteins that control transcription of small subsets of genes, and these have been called specialized NusGs (NusG SP s) (215). The best characterized NusG SP is RfaH, which is involved in the control of transcription of genes required for extracytoplasmic functions such as lipopolysaccharide (LPS) synthesis, toxin production, and phage sensitivity (216).…”

Ratcheting of RNA polymerase toward structural principles of RNA polymerase operations

“…NusG is also known as the EC interface for the interactions with the ribosome and Rho. 29 RfaH reportedly serves as a physical bridge between RNAP and ribosome, facilitating expression of horizontally transferred genes. 30 The translating ribosome may cooperate with NusG/RfaH to maintain the closed-clamp tight form during the translation-coupled transcription, whereas Rho should counteract NusG to destabilize the closed-clamp tight form for termination.…”