RNA polymerase-binding protein A (RbpA)

RNA polymerase-binding protein A (RbpA) is an essential, actinobacteria-specific transcription factor that plays a critical role in the growth and survival of pathogens such as Mycobacterium tuberculosis. It functions as a non-DNA-binding activator that associates with the RNA polymerase (RNAP) core enzyme and recruits the principal sigma factor (SigA) to stabilize transcription initiation complexes at vegetative promoters. RbpA is notably involved in modulating the bacterial response to the frontline antibiotic rifampicin, where it can confer basal levels of resistance by stabilizing the RNAP-promoter complex even in the presence of the drug. Because RbpA is essential for mycobacterial viability and has no human homolog, it is considered a high-priority therapeutic target for the development of next-generation anti-tubercular agents. Current drug discovery efforts are focused on identifying small molecules or peptides that disrupt the essential protein-protein interaction between RbpA and the RNAP subunits.

Other names

RbpARNA polymerase-binding protein RbpARv2050RNA polymerase-binding protein

Experimental drugs aim to inhibit the protein-protein interaction between RbpA and the RNA polymerase core subunits (specifically the β and α subunits), thereby preventing the stabilization of the transcription initiation complex and disrupting bacterial gene expression.