RNA polymerase II elongation complex (Pol II EC)

The elongating phosphorylated RNA polymerase II complex is the multi-subunit machinery responsible for the synthesis of messenger RNA (mRNA) in eukaryotic cells. It is defined by the specific phosphorylation of the C-terminal domain (CTD) of its largest subunit, RPB1, typically at Serine 2 (Ser2) and Serine 5 (Ser5) residues (Harlen & Churchman, 2017, Nature Reviews Molecular Cell Biology). This phosphorylation, mediated by kinases such as CDK7 and CDK9, facilitates the transition from transcription initiation to productive elongation and coordinates the recruitment of RNA processing factors (Zaborowska et al., 2016, Transcription). In oncology, many aggressive tumors exhibit transcriptional addiction, where they rely on the continuous activity of this complex to maintain high levels of short-lived oncogenic proteins like MYC and MCL1 (Kwiatkowski et al., 2014, Nature). Therapeutic interventions often target the regulatory kinases, such as CDK9 inhibitors like Alvocidib, or use covalent inhibitors like THZ1 to disrupt the complex's assembly and function. While effective in preclinical models, targeting this fundamental process poses significant safety challenges due to the potential for widespread disruption of normal cellular homeostasis (UniProt P24928).

Other names

Phosphorylated RNA polymerase IIRNAPII elongation complexActive transcription complexp-Pol IIDNA-directed RNA polymerase II complex

Inhibition of cyclin-dependent kinases (CDKs) such as CDK7 and CDK9 that phosphorylate the C-terminal domain (CTD) of RPB1, or direct physical blockage of the polymerase translocation along the DNA template.