title: Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the σ A-containing RNA polymerase holoenzyme.
abstract: RbpA is an RNA polymerase (RNAP)-binding protein whose presence increases the tolerance levels of Mycobacteria to the first-line anti-tuberculosis drug rifampicin by an unknown mechanism. Here, we show that the role of Mycobacterium tuberculosis RbpA in resistance is indirect because it does not affect the sensitivity of RNAP to rifampicin while it stimulates transcription controlled by the housekeeping σ(A)-factor. The transcription regulated by the stress-related σ(F) was not affected by RbpA. The binding site of RbpA maps to the RNAP β subunit Sandwich-Barrel Hybrid Motif, which has not previously been described as an activator target and does not overlap the rifampicin binding site. Our data suggest that RbpA modifies the structure of the core RNAP, increases its affinity for σ(A) and facilitates the assembly of the transcriptionally competent promoter complexes. We propose that RbpA is an essential partner which advantages σ(A) competitiveness for core RNAP binding with respect to the alternative σ factors. The RbpA-driven stimulation of the housekeeping gene expression may help Mycobacteria to tolerate high rifampicin levels and to adapt to the stress conditions during infection.
authors.affiliation: CNRS UMR 5236 - UM1 - UM2, Centre d'études d'agents Pathogénes et Biothechnologies pour la Santé (CPBS), 1919 route de Mende, 34293 Montpellier, France.
authors.forename: Yangbo
authors.initials: Y
authors.lastname: Hu
authors.forename: Zakia
authors.initials: Z
authors.lastname: Morichaud
authors.forename: Shiyun
authors.initials: S
authors.lastname: Chen
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Leonetti
authors.forename: Konstantin
authors.initials: K
authors.lastname: Brodolin
mesh_terms: D020816:Amino Acid Motifs; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020035:Holoenzymes / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics*; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D012293:Rifampin / Q000494:pharmacology; D012808:Sigma Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000904:Antibiotics, Antitubercular; D001426:Bacterial Proteins; D020035:Holoenzymes; D012808:Sigma Factor; D015534:Trans-Activators; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin