Mycobacterial RNA polymerase (RNAP)

**Mycobacterial RNA polymerase (RNAP)** is a multi-subunit enzyme (~400 kDa) fundamental for the transcription of DNA into RNA in mycobacteria, including *Mycobacterium tuberculosis* (Mtb)[1][6][9]. It is composed of five core subunits (two α, β, β′, and ω), forming a claw-like structure that binds DNA for RNA synthesis initiation, elongation, and termination[1][3]. Unlike eukaryotes, which use multiple specialized polymerases, bacteria—including Mtb—use a singular RNAP for all classes of RNA transcripts[4][9]. The Mtb RNAP displays distinct structural and regulatory features compared to other bacteria; for example, it interacts with specific transcription factors such as CarD and RbpA, which are essential for transcriptional regulation and pathogen survival, and these unique properties can be targeted for drug development[1][2][5][6][7]. RNAP is the molecular target of rifampicin, a first-line antibiotic in tuberculosis therapy, but resistance has driven urgent interest in novel RNAP inhibitors and a deeper understanding of its mechanisms[2][4][6]. RNAP activity is essential for mycobacterial growth and viability, making it a validated and high-value drug target to combat tuberculosis infection and drug-resistant strains[2][4][6][9].

Other names

Bacterial DNA-dependent RNA polymeraseMtb RNA polymeraseMTB RNAP

Inhibition of bacterial transcription (Rifampicin binds to the β subunit and inhibits RNA synthesis) Disruption of RNAP/transcription factor (CarD) interactions inhibits enzyme activity and thus prevents gene expression[2][4][6]