DNA-directed RNA polymerase II complex (RNAP II) (RNAP II)

DNA-directed RNA polymerase II complex (RNAP II) is a multi-subunit enzyme responsible for the transcription of DNA into messenger RNA (mRNA) and most small nuclear RNAs in eukaryotic cells (UniProt, 2023). It serves as the central engine of the transcriptional machinery, requiring the assembly of general transcription factors to form a pre-initiation complex at gene promoters (Nature Reviews Molecular Cell Biology, 2020). The activity and processivity of the complex are tightly regulated by the phosphorylation of the C-terminal domain (CTD) of its largest subunit, RPB1, which coordinates transcription stages and RNA processing (Cell, 2018). In various pathologies, particularly oncology, RNAP II is frequently dysregulated or hijacked by oncogenic drivers like MYC to sustain the high transcriptional demands of rapid cell proliferation (Cancer Cell, 2021). Therapeutic targeting of the complex, such as with the drug lurbinectedin, often involves inducing the degradation of the RPB1 subunit or stalling the polymerase on the DNA template (Clinical Cancer Research, 2019). While effective in treating certain cancers like small cell lung cancer, targeting this fundamental cellular component presents significant safety challenges, including potential for systemic toxicity and a narrow therapeutic window (Journal of Biological Chemistry, 2022).

Other names

RNA polymerase IIPol IIRNA polymerase BRNAP2RNA polymerase II holoenzyme

Inhibition of RNA synthesis through DNA minor groove binding, induction of RPB1 subunit degradation, or blocking of the nucleotide addition cycle (Nature, 2018; Clinical Cancer Research, 2019).