NusGfamily

NusGfamily refers to a conserved group of transcription elongation factors that regulate RNA synthesis in bacteria and, more distantly, in archaea and eukaryotes. The best-known members are NusG and its paralog RfaH in bacteria, while archaeal and eukaryotic lineages possess homologs such as Spt5 (often in complex with Spt4). NusG family proteins influence transcription elongation, pausing, termination, and transcription-translation coupling by engaging RNA polymerase and, in many cases, recruiting additional factors or bridging to the ribosome.

Structural characteristics of NusG family proteins typically involve an N-terminal domain that docks onto RNA polymerase and a C-terminal domain that mediates interactions with partner factors. In many bacterial NusG proteins, the C-terminal domain is a KOW module that supports binding to either the ribosome or termination factors such as Rho. The paralog RfaH is a specialized NusG variant with a regulatory C-terminal region that can autoinhibit the RNAP-binding surface; upon activation by an ops DNA sequence, RfaH adopts a conformation that enables productive anti-termination and enhanced processivity on select operons.

Functional scope and regulatory modes vary within the family. NusG generally promotes transcriptional processivity and modulates pausing, and it can participate in Rho-dependent termination in operons where termination is favored. RfaH acts as an anti-terminator, enabling transcription through long operons with reduced pausing and termination, and it can influence transcription-translation coupling by coordinating interactions with the translational machinery.

Evolutionary context highlights the widespread presence of NusG-like proteins across bacteria, with paralogs such as RfaH, and the representation of NusG homologs in archaea and eukaryotes as Spt5 (often with Spt4), reflecting deep conservation of transcription control mechanisms.