DNA-directed RNA polymerase III (Pol III) (Pol III)

DNA-directed RNA polymerase III (Pol III) is a complex multi-subunit enzyme responsible for the transcription of essential non-coding RNAs, such as transfer RNA (tRNA) and 5S ribosomal RNA (rRNA), which are critical for protein synthesis and cellular homeostasis (UniProt: P05423). Along with RNA polymerase I and II, it forms the core machinery for gene expression in eukaryotes. Pol III activity is tightly regulated by tumor suppressors like p53 and RB, and its dysregulation is a hallmark of many cancers where it is upregulated to support rapid cell proliferation (PubMed: 21572442). Mutations in the subunits of Pol III, particularly POLR3A and POLR3B, are associated with severe neurodegenerative conditions like hypomyelinating leukodystrophy (PubMed: 21763480). Pharmacological targeting of Pol III is difficult due to its essential nature; however, small molecules like ML-60218 have been identified as specific inhibitors for research purposes (PubChem: CID 2826651). Other broader inhibitors, such as alpha-amanitin, target both Pol II and Pol III, leading to high toxicity, which limits their clinical utility but makes them significant in toxicological contexts (StatPearls: NBK431050).

Other names

RNA polymerase IIIPol IIIDNA-directed RNA polymerase III complexPOLR3RNA polymerase IRNA polymerase IIDNA-directed RNA polymerase

Inhibition of DNA-directed RNA polymerase activity, typically by binding to the active site or blocking the translocation of the enzyme along the DNA template, thereby halting the synthesis of RNA transcripts (PubMed: 115149).