RNA polymerase and RNA synthetic machinery (RNAP) (RNAP)

RNA polymerase (RNAP) is the fundamental enzyme complex responsible for transcription, the process of synthesizing RNA from a DNA or RNA template [3]. In bacteria, the core RNAP is a multi-subunit enzyme that serves as a primary target for antibiotics like rifampicin, which binds to the beta subunit to sterically block the elongation of the nascent RNA chain [1]. Viral pathogens often utilize an RNA-dependent RNA polymerase (RdRp) for genome replication, making it a critical target for antivirals such as remdesivir and sofosbuvir, which act as nucleoside analogs to terminate RNA synthesis [2, 4]. Beyond infectious diseases, human RNA polymerases (I, II, and III) are increasingly recognized as therapeutic targets in oncology because malignant cells often depend on hyperactivated transcription for rapid proliferation [5]. The broader "RNA synthetic machinery" includes various transcription factors, sigma factors, and co-activators that coordinate the initiation and regulation of this process. Drugs targeting these systems must achieve high selectivity to avoid interfering with essential host cell transcription, which is a major challenge in drug development. Resistance often arises through specific mutations in the polymerase subunits, such as the rpoB gene in Mycobacterium tuberculosis [1]. Monitoring viral or bacterial load serves as a primary biomarker for the efficacy of these inhibitors in clinical settings [2].

Other names

RNAPDNA-directed RNA polymeraseRNA-dependent RNA polymeraseRdRpTranscriptaseRNA synthetic complex

Inhibition of RNA synthesis through various mechanisms including blocking the RNA exit channel (e.g., rifamycins), competitive inhibition of nucleotide incorporation, or inducing premature chain termination (e.g., remdesivir) [1, 2].