The transcript cleavage factor paralogue TFS4 is a potent RNA polymerase inhibitor

Nat Commun. 2017 Dec 4;8(1):1914. doi: 10.1038/s41467-017-02081-3.


TFIIS-like transcript cleavage factors enhance the processivity and fidelity of archaeal and eukaryotic RNA polymerases. Sulfolobus solfataricus TFS1 functions as a bona fide cleavage factor, while the paralogous TFS4 evolved into a potent RNA polymerase inhibitor. TFS4 destabilises the TBP-TFB-RNAP pre-initiation complex and inhibits transcription initiation and elongation. All inhibitory activities are dependent on three lysine residues at the tip of the C-terminal zinc ribbon of TFS4; the inhibition likely involves an allosteric component and is mitigated by the basal transcription factor TFEα/β. A chimeric variant of yeast TFIIS and TFS4 inhibits RNAPII transcription, suggesting that the molecular basis of inhibition is conserved between archaea and eukaryotes. TFS4 expression in S. solfataricus is induced in response to infection with the S ulfolobus turreted icosahedral virus. Our results reveal a compelling functional diversification of cleavage factors in archaea, and provide novel insights into transcription inhibition in the context of the host-virus relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • RNA Polymerase II / antagonists & inhibitors*
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sulfolobus solfataricus / metabolism*
  • Transcription Factor TFIIB / metabolism
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII / metabolism
  • Transcription, Genetic
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • SUA7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Tfs1 protein, S cerevisiae
  • Transcription Factor TFIIB
  • Transcription Factors
  • Transcription Factors, TFII
  • mRNA Cleavage and Polyadenylation Factors
  • transcription factor TFIIE
  • RNA Polymerase II