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The RNA polymerase and RNA processing machinery represent a complex network of enzymes and proteins responsible for the synthesis and maturation of RNA molecules. In bacteria, the DNA-directed RNA polymerase (RNAP) is a multi-subunit enzyme that serves as the primary target for the rifamycin class of antibiotics, which bind the beta-subunit to block the exit path of the nascent RNA [1]. In viruses, RNA-dependent RNA polymerases (RdRp) are essential for genome replication and are targeted by nucleoside and nucleotide analogs such as remdesivir and sofosbuvir, which act as chain terminators [2]. The RNA processing component includes the spliceosome, capping enzymes, and polyadenylation factors, which are critical for eukaryotic gene expression and are increasingly targeted in cancer therapy to exploit splicing vulnerabilities [3]. Drugs interacting with this machinery often function by inhibiting enzymatic activity, inducing lethal mutagenesis, or disrupting protein-protein interactions within the complex [4]. However, the high degree of conservation in these systems poses significant safety challenges, including potential cross-reactivity with host mitochondrial polymerases and associated toxicities [5].
Inhibition of RNA synthesis, RNA chain termination, and modulation of RNA splicing.
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