Target intelligence / Profile preview

RNA polymerase II elongation complex (Pol II EC) (Pol II EC)

Target
Pol II EC
Molecular classification
Enzyme, Multi-protein complex, Transcription factor, RNA polymerase
01

Overview

The RNA polymerase II elongation complex (Pol II EC) is a highly regulated multi-protein assembly responsible for the processive synthesis of messenger RNA (mRNA) from a DNA template [4, 6]. It is a ternary complex composed of the 12-subunit RNA polymerase II enzyme, a DNA template, and a nascent RNA transcript, often working in concert with various elongation factors such as P-TEFb, DSIF, and the Super Elongation Complex (SEC) [1, 14]. The activity and processivity of the complex are primarily controlled through the dynamic phosphorylation of the C-terminal domain (CTD) of its largest subunit, RPB1, which serves as a scaffold for RNA processing and chromatin-modifying enzymes [11, 12]. Dysregulation of Pol II elongation is frequently observed in human diseases, particularly in cancers where it drives the overexpression of oncogenes like MYC, and in viral infections such as HIV-1, which hijacks the complex for viral genome expression [2, 10, 13]. Therapeutic targeting of the Pol II EC involves direct inhibitors like alpha-amanitin or small molecules that target associated regulatory kinases and elongation factors to selectively suppress pathological gene expression [1, 13].

Other names
RNA polymerase II transcription elongation complexPol II elongation complexRNAP II elongation complexTernary elongation complexRNA polymerase II productive elongation complex
02

Mechanism of action

Inhibition of RNA synthesis through direct binding to the polymerase active site, inhibition of C-terminal domain (CTD) phosphorylation via CDK9/CDK7 antagonism, induction of RNA polymerase II degradation, and transcriptional arrest at DNA lesions or intercalated sites.

03

Biological functions

TranscriptionRNA processingGene expression regulationDNA repairChromatin remodeling
04

Disease associations

CancerViral infectionInflammationGenetic disordersNeurodegenerative disease
05

Safety considerations

HepatotoxicityNephrotoxicityNeutropeniaGeneral systemic toxicity due to inhibition of essential gene transcriptionGastrointestinal toxicity
06

Interacting drugs

Alpha-amanitin

7 more in the full profile.

07

Biomarkers

Phospho-RNA polymerase II (Ser2)Phospho-RNA polymerase II (Ser5)MYC mRNA levelsNascent RNA transcript levels (mNET-seq/PRO-seq)

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