Transcription factor S-II (TFIIS) induces mRNA cleavage by enhancing the intrinsic nuclease activity of RNA polymerase (Pol) II, past template-encoded pause sites. It is widely distributed being found in mammals, Drosophila, yeast and in the archaebacteria Sulfolobus acidocaldarius [1]. S-II proteins have a relatively conserved C-terminal region but variable N-terminal region, and some members of this family are expressed in a tissue-specific manner [2, 3].

TFIIS is a modular factor that comprises an N-terminal domain I, a central domain II, and a C-terminal domain III [4]. The weakly conserved domain I forms a four-helix bundle and is not required for TFIIS activity. Domain II forms a three-helix bundle, and domain III adopts a zinc-ribbon fold with a thin protruding beta-hairpin. Domain II and the linker between domains II and III are required for Pol II binding, whereas domain III is essential for stimulation of RNA cleavage. TFIIS extends from the polymerase surface via a pore to the internal active site, spanning a distance of 100 Angstroms. Two essential and invariant acidic residues in a TFIIS loop complement the Pol II active site and could position a metal ion and a water molecule for hydrolytic RNA cleavage. TFIIS also induces extensive structural changes in Pol II that would realign nucleic acids in the active centre.

1. Putative tfIIs gene of Sulfolobus acidocaldarius encoding an archaeal transcription elongation factor is situated directly downstream of the gene for a small subunit of DNA-dependent RNA polymerase. Nucleic Acids Res. 21, 2251
2. Heterogeneity and tissue-specific expression of eukaryotic transcription factor S-II-related protein mRNA. J. Biochem. 109, 674-7
3. Isolation and characterization of a cDNA encoding a new type of human transcription elongation factor S-II. Gene 167, 297-302
4. Architecture of the RNA polymerase II-TFIIS complex and implications for mRNA cleavage. Cell 114, 347-57

Transcription factor S-II (TFIIS) induces mRNA cleavage by enhancing the intrinsic nuclease ac
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