DNA-dependent RNA polymerase I (Pol I)

DNA-dependent RNA polymerase I (Pol I) is a specialized multi-subunit enzyme complex located in the nucleolus, where it is responsible for the transcription of the 45S/47S ribosomal RNA (rRNA) precursor [NIH, 2018]. This precursor is subsequently processed into the 18S, 5.8S, and 28S rRNAs, which serve as the structural and catalytic core of ribosomes [Wikipedia, 2024]. Pol I activity is the rate-limiting step in ribosome biogenesis and is tightly coupled to cellular growth and proliferation signals [NIH, 2021]. In many types of cancer, Pol I transcription is constitutively upregulated to meet the high demand for protein synthesis required for rapid cell division [MDPI, 2022]. Consequently, Pol I has emerged as a promising therapeutic target in oncology, with small-molecule inhibitors like CX-5461 and BMH-21 designed to selectively block rRNA synthesis and induce nucleolar stress-mediated apoptosis [PubMed, 2014; NIH, 2017]. Beyond its role in cancer, genetic mutations in Pol I subunits are associated with ribosomopathies such as Treacher Collins syndrome, underscoring its fundamental importance in human development and homeostasis [NIH, 2021].

Other names

RNA polymerase IRNAP IDNA-directed RNA polymerase IRNA nucleotidyltransferase (DNA-directed) IPolR1

Inhibition of ribosomal RNA (rRNA) synthesis through various mechanisms, including disruption of the pre-initiation complex (e.g., CX-5461), intercalation into GC-rich rDNA (e.g., BMH-21), or stabilization of G-quadruplexes (e.g., Quarfloxin), ultimately leading to nucleolar stress and cell cycle arrest or apoptosis [PubMed, 2014; NIH, 2017].