Spt5

Spt5 is a transcription elongation factor that binds RNA polymerase and modulates the elongation phase of transcription. In eukaryotes it forms the DSIF complex with Spt4; in bacteria and archaea there are homologs—NusG in bacteria and Spt5-like proteins in archaea. Spt5 is conserved across life, with a characteristic domain structure that supports interactions with the polymerase and nucleic acids, and in many multicellular eukaryotes a C-terminal repeat domain that is subject to regulatory phosphorylation.

Structurally, Spt5 contains an N-terminal NGN domain that anchors to RNA polymerase, followed by a series of KOW domains that mediate interactions with nucleic acids and other factors. In many eukaryotes, a C-terminal repeat domain contributes regulatory control and phosphorylation sites that influence activity. Bacterial NusG, by contrast, typically lacks the extended CTR found in many eukaryotic Spt5 proteins.

Functionally, Spt5 is central to transcription elongation control. In eukaryotes, DSIF and the Negative Elongation Factor (NELF) induce promoter-proximal pausing shortly after initiation. Productive elongation requires P-TEFb (a CDK9-cyclin complex)–mediated phosphorylation of Spt5 and NELF, which releases the pause and promotes processive transcription and coordination with RNA processing. Spt5 also influences polymerase processivity and recruitment of capping enzymes. In bacteria, NusG and Spt5 homologs interact with RNA polymerase to modulate pausing and termination, and can affect antitermination pathways; in archaea, Spt4/5 performs a similar elongation role with RNA polymerase.

Spt5 is essential for viability in many organisms and is a key regulator of transcriptional elongation, pausing dynamics, and coordination with RNA processing.