A regulatory protein that interferes with activator-stimulated transcription in bacteria

Transcriptional activator proteins in bacteria often operate by interaction with the C-terminal domain of the alpha-subunit of RNA polymerase (RNAP). Here we report the discovery of an anti-alpha factor Spx in Bacillus subtilis that blocks transcriptional activation by binding to the alpha-C-terminal domain, thereby interfering with the capacity of RNAP to respond to certain activator proteins. Spx disrupts complex formation between the activator proteins ResD and ComA and promoter-bound RNAP, and it does so by direct interaction with the alpha-subunit. ResD- and ComA-stimulated transcription requires the proteolytic elimination of Spx by the ATP-dependent protease ClpXP. Spx represents a class of transcriptional regulators that inhibit activator-stimulated transcription by interaction with alpha.