NusG, an Ancient Yet Rapidly Evolving Transcription Factor

Abstract

Timely and accurate RNA synthesis depends on accessory proteins that instruct RNA polymerase (RNAP) where and when to start and stop transcription. Among thousands of transcription factors, NusG/Spt5 stand out as the only universally conserved family of regulators. These proteins interact with RNAP to promote uninterrupted RNA synthesis and with diverse cellular partners to couple transcription to RNA processing, modification or translation, or to trigger premature termination of aberrant transcription. NusG homologs are present in all cells that utilize bacterial-type RNAP, from endosymbionts to plants, underscoring their ancient and essential function. Yet, in stark contrast to other core RNAP components, NusG family is actively evolving: horizontal gene transfer and sub-functionalization drive emergence of NusG paralogs, such as bacterial LoaP, RfaH, and UpxY. These specialized regulators activate a few (or just one) operons required for expression of antibiotics, capsules, secretion systems, toxins, and other niche-specific macromolecules. Despite their common origin and binding site on the RNAP, NusG homologs differ in their target selection, interacting partners and effects on RNA synthesis. Even among housekeeping NusGs from diverse bacteria, some factors promote pause-free transcription while others slow the RNAP down. Here, we discuss structure, function, and evolution of NusG proteins, focusing on unique mechanisms that determine their effects on gene expression and enable bacterial adaptation to diverse ecological niches.

Early Evolution of Transcription Systems and Divergence of Archaea and Bacteria

“…During transcription elongation, TFB and σ factors cycle off RNAP and are replaced by the elongation factor homologs Spt5/Spt4 in Archaea and NusG in Bacteria ( Werner, 2012 ; Blombach et al, 2013 ; Hartzog and Fu, 2013 ; Tomar and Artsimovitch, 2013 ; Yakhnin and Babitzke, 2014 ; Wang and Artsimovitch, 2020 ). These elongation factors occupy approximately the same positions on RNAP as HTH2 and HTH3 of bacterial σA (not shown).…”

Transcription complexes as RNA chaperones

“…λN achieves this large-scale repositioning of NusA by acting as a molecular glue that rewires Nus-factor interactions, thereby concomitantly subverting regular activities of the other Nus factors as well. NusG and relatives represent the only transcription factor family that is universally conserved across bacteria, archaea and eukaryotes [ 132 ]. E. coli NusG is a two-domain protein [ 133 ].…”

Mechanism of transcription modulation by the transcription-repair coupling factor

“…Rescue from such backtracked states is catalyzed by processivity factors such as GreA and GreB (Abdelkareem et al, 2019;Borukhov et al, 1993). Elongation is modulated by the universally conserved elongation/pause factor, the bacterial NusG, homologous with Spt5 in eukaryotes (reviewed by (Wang and Artsimovitch, 2020)). In Escherichia coli, NusG maintains processive transcription (Burova et al, 1995) by suppressing backtracking through contacts on the upstream DNA (Herbert et al, 2010;Kang et al, 2018).…”