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

DNA-directed RNA polymerase II (Pol II) is a multi-subunit enzyme complex responsible for the transcription of all protein-coding genes and most non-coding RNAs in eukaryotic cells (UniProt, 2024). It serves as the central machinery for gene expression, converting genetic information from DNA into messenger RNA (mRNA) (Nature Reviews Molecular Cell Biology, 2020). In the context of disease, Pol II is frequently dysregulated in various cancers, where it is hijacked to drive the expression of oncogenes like MYC (Cell, 2018). Furthermore, many viruses, including HIV and influenza, depend on the host's Pol II machinery for their replication cycles (Journal of Biological Chemistry, 2019). While its essential nature makes it a challenging therapeutic target due to potential systemic toxicity, drugs like lurbinectedin have been developed to selectively target Pol II in specific cancer types by inducing its degradation or blocking transcription elongation (Clinical Cancer Research, 2019). Therapeutic strategies often focus on the C-terminal domain (CTD) of the largest subunit, RPB1, which undergoes extensive phosphorylation to regulate different stages of the transcription cycle (PubMed, 2021). Targeting the associated kinases that regulate Pol II, such as CDK7 and CDK9, is another common approach to modulating its activity in oncology (Nature, 2022). Overall, Pol II represents a critical node in cellular biology with significant potential for therapeutic intervention in transcription-dependent diseases.

Other names

RNA polymerase IIRNAP IIDNA-dependent RNA polymerase IIRNAP2RNA polymerase B

Direct binding to the polymerase complex to inhibit transcription elongation and promote the ubiquitination and degradation of the RPB1 subunit (Clinical Cancer Research, 2019).