The crenarchaeal DNA damage-inducible transcription factor B paralogue TFB3 is a general activator of transcription.

Transcription initiation factor B (TFB) is conserved in eukaryotes and archaea and has an essential role in the recruitment of RNA polymerase to the promoter and the initiation of transcription. The genome of Sulfolobus solfataricus and related crenarchaea contain three paralogues of the tfb gene. Two of them (tfb1 and tfb2) encode full-length TFB proteins. The third (tfb3) is significantly shorter than the other two, possessing an N-terminal Zn ribbon domain but lacking the B-finger and DNA binding domains. In S. solfataricus and Sulfolobus acidocaldarius, tfb3 is one of the most highly upregulated transcripts following exposure to UV irradiation. We demonstrate that S. solfataricus TFB3 binds to the RpoK subunit of RNA polymerase, an interaction dependent on the Zn ribbon motif of TFB3. TFB3 can also interact with the ternary complex of TBP and TFB1 bound to a DNA promoter. TFB3 stimulates transcription in vitro from several promoters in the presence of TFB1 and TBP. These observations are consistent with a model whereby TFB3 activates general transcription in trans, via an interaction with RNA polymerase in the pre-initiation complex. This could provide a mechanism for the modulation of transcription initiation in response to environmental stresses, such as DNA damage.