TFIIS

TFIIS, or transcription elongation factor IIS, is a conserved eukaryotic protein that assists RNA polymerase II during transcription elongation. By stimulating the polymerase’s intrinsic RNA cleavage activity, TFIIS enables the enzyme to recover from backtracking and resume RNA synthesis after pausing or arrest.

Mechanistically, TFIIS binds to RNA polymerase II near the active site and promotes hydrolytic cleavage of the nascent RNA protruding from the backtracked complex. The new RNA 3′ end realigns in the active site, allowing elongation to continue. The cleavage reaction relies on conserved acidic residues that form a catalytic center within TFIIS, typically organized in a tripartite domain structure.

TFIIS proteins generally comprise three conserved domains. Domain I engages the polymerase, Domain II contains the acidic motif responsible for catalysis, and Domain III helps position the RNA and stabilize the active complex. In many species, the protein is acidic in its central region and functions in the nucleus without transmembrane segments.

In humans, several paralogs encode TFIIS-like proteins. The canonical factor is TCEA1, which is broadly expressed, while TCEA2 and TCEA3 show tissue-restricted expression and may substitute or modulate function in specific cell types or developmental contexts. The proteins are evolutionarily related to the yeast DST1 gene and are broadly conserved across eukaryotes.

TFIIS contributes to transcriptional fidelity and efficiency and has been implicated in transcription-coupled DNA repair and stress responses, where rapid resumption of transcription is advantageous. It also influences promoter-proximal pausing and may interact with other elongation factors to regulate transcription dynamics.