RNA polymerase–mediated RNA incorporation sites

RNA polymerase–mediated RNA incorporation sites refer to the catalytic active centers within RNA polymerase enzymes where ribonucleoside triphosphates (rNTPs) are selected and covalently added to a growing RNA chain. These sites are found in various classes of polymerases, including viral RNA-dependent RNA polymerases (RdRp), eukaryotic RNA polymerase II, and mitochondrial RNA polymerase (POLRMT). In the context of drug development, these sites are the primary targets for nucleoside and nucleotide analogs, which compete with natural substrates to be incorporated into the nascent RNA strand. Once incorporated, these analogs can cause premature chain termination, lethal mutagenesis, or delayed elongation, effectively inhibiting viral replication or cellular transcription. Understanding the structural and kinetic properties of these incorporation sites is critical for designing potent antivirals and chemotherapeutic agents while minimizing off-target toxicity to human polymerases.

Other names

RNA polymerase active siteRNA polymerase elongation complexRibonucleotide incorporation siteTranscription active siteNascent RNA incorporation site