DNA-directed RNA polymerase I and II (Pol I/II)

Eukaryotic RNA polymerases I and II are essential multi-subunit enzymes that catalyze the transcription of DNA into RNA. RNA polymerase I (Pol I) is dedicated to synthesizing the 45S precursor of ribosomal RNA (rRNA), which is the rate-limiting step in ribosome biogenesis and a key determinant of cellular growth capacity [UniProt P19387]. RNA polymerase II (Pol II) is responsible for transcribing all protein-coding genes into messenger RNA (mRNA), as well as various non-coding RNAs, making it the primary mediator of the cell's genetic program [UniProt P24928]. In oncology, these polymerases are frequently hijacked or hyperactivated to support the rapid proliferation of malignant cells, often under the control of the c-Myc oncogene [Bywater et al., 2013]. Therapeutic strategies targeting Pol I, such as the small molecule CX-5461, aim to selectively disrupt rRNA synthesis to trigger nucleolar stress and p53-mediated apoptosis in cancer cells [Drygin et al., 2011]. Conversely, Pol II is targeted by potent toxins like alpha-amanitin and experimental drugs like triptolide, which inhibit global transcription [Bushnell et al., 2002]. While effective at halting tumor growth, the fundamental necessity of these enzymes for normal cell function poses significant risks for systemic toxicity and requires precise therapeutic windows.

Other names

RNA polymerase IRNA polymerase IIRNAP IRNAP IIDNA-directed RNA polymerase IDNA-directed RNA polymerase IIPol IPol II

Inhibition of RNA polymerase catalytic activity, DNA binding, or recruitment of essential transcription factors, leading to the suppression of rRNA (Pol I) and mRNA (Pol II) synthesis [Drygin et al., 2011; Bushnell et al., 2002].