Mycobacterium tuberculosis RNA polymerase (RNAP)

Mycobacterium tuberculosis RNA polymerase is a multi-subunit enzyme complex responsible for catalyzing the transcription of DNA into RNA in mycobacteria. The enzyme consists of a core (α₂ββ'ω), which assembles with a sigma factor to form the transcriptionally competent holoenzyme. Mtb RNA polymerase is structurally distinct from eukaryotic polymerases and exhibits unique insertions and regulatory protein interactions compared to other bacteria, contributing to the pathogen’s adaptation and persistence[1][3][5]. The enzyme is essential for bacterial survival and is the primary molecular target of rifampin and related first-line antibiotics used in the treatment of tuberculosis. Resistance largely results from mutations in the rpoB gene. Recent work also targets RNAP-protein interactions, such as with CarD, as novel antibacterial strategies[4][6][7][9]. Structural peculiarities, such as the taxon-specific β′ subunit insertion that stabilizes the open promoter complex, are under active investigation for drug development. RNAP is regulated by multiple transcription factors (e.g., CarD, RbpA), which modulate its activity under various stress and environmental conditions, underpinning its centrality in the control of gene expression and adaptation of M. tuberculosis.

Other names

Mycobacterial RNA polymeraseMtb RNAPDNA-dependent RNA polymerase (Mycobacterium tuberculosis)bacterial RNAP (Mycobacterium)

Rifampin and analogs: Bind to the β-subunit of RNAP, block the DNA/RNA channel, and inhibit the initiation of RNA synthesis, leading to suppression of Mtb transcription and death of the bacterium[5][7][9]. Peptide-based inhibitors (experimental): Disrupt the interaction between RNAP β-subunit and transcription factors such as CarD, affecting transcription regulation and survival[4].