RNA polymerase II transcriptional machinery (Pol II)

The RNA polymerase II (Pol II) transcriptional machinery is a massive multi-protein assembly responsible for the transcription of protein-coding genes into messenger RNA (mRNA) in eukaryotic cells (Young, 1991 [5]). The core of this machinery is the 12-subunit RNA polymerase II enzyme, which works in tandem with general transcription factors (GTFs) such as TFIID, TFIIB, and TFIIH to form the pre-initiation complex at gene promoters (Sainsbury et al., 2015 [2]). Dysregulation of Pol II activity is a hallmark of various cancers, where it is often recruited to super-enhancers to drive the over-expression of key oncogenic drivers like MYC (Bradner et al., 2017 [6]). Therapeutic targeting of the Pol II machinery involves diverse strategies, including direct inhibition of the polymerase's catalytic site, induction of RPB1 subunit degradation, or the inhibition of regulatory kinases like CDK7 and CDK9 that control the transition from initiation to elongation (Kwiatkowski et al., 2014 [4]). While its essential nature in all cells poses significant safety risks, the transcriptional addiction of malignant cells provides a window for clinical intervention, as seen with the approval of agents like lurbinectedin for small cell lung cancer (Trigo et al., 2020 [3]). Sources: [1] UniProt (P24928); [2] Nature Reviews Molecular Cell Biology (2015, 16:129-143); [3] The Lancet Oncology (2020, 21:645-654); [4] Nature (2014, 511:616-620); [5] Annual Review of Biochemistry (1991, 60:689-703); [6] Cell (2017, 168:629-643).

Other names

RNAP IIDNA-directed RNA polymerase II complexRNA polymerase BPol II core enzymeRNA polymerase II holoenzyme

Inhibition of the catalytic activity of the RNA polymerase II complex, degradation of the RPB1 subunit, or inhibition of the cyclin-dependent kinases (e.g., CDK7, CDK9) that phosphorylate the C-terminal domain (CTD) to regulate transcriptional transition and elongation.