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

DNA-directed RNA polymerase III (Pol III) is a complex, 17-subunit enzyme responsible for the transcription of essential small, non-coding RNAs, including transfer RNAs (tRNAs), 5S ribosomal RNA (rRNA), and U6 small nuclear RNA [UniProt: P05423, PubMed: 22225831]. It plays a pivotal role in cellular homeostasis by regulating the supply of components necessary for protein synthesis and is tightly controlled by major growth-signaling pathways [PubMed: 20159563]. Dysregulation of Pol III is a hallmark of many cancers, where its activity is often hijacked by oncogenic proteins to support the high metabolic demands of tumor growth [PubMed: 28220037]. Beyond oncology, genetic mutations in Pol III subunits lead to severe neurodegenerative conditions, such as hypomyelinating leukodystrophy, highlighting its importance in nervous system development [PubMed: 21741540]. The complex is also a significant target in autoimmune diseases; specifically, anti-Pol III antibodies are diagnostic for systemic sclerosis and are linked to rapid skin thickening and renal crisis [PubMed: 20635355]. While direct therapeutic targeting of Pol III is challenging due to its essential nature, small-molecule inhibitors like ML-60218 are being explored for their potential to selectively curb the hypertrophic transcription seen in cancer cells [PubMed: 17110398].

Other names

RNA polymerase IIIRNAP IIIPol III complexDNA-directed RNA polymerase III

Inhibition of RNA synthesis by binding to the catalytic core or interfering with promoter recruitment and assembly of the transcription initiation complex [PubMed: 17110398, PubMed: 22225831].