Integrator complex (INT)

The Integrator complex is a large, evolutionarily conserved multi-subunit protein assembly, typically comprising at least 14 subunits (INTS1–INTS14), that plays a pivotal role in RNA processing and transcriptional regulation (PMID: 16239144). Originally identified for its essential function in the 3-end cleavage of spliceosomal small nuclear RNAs (snRNAs) U1 and U2, it has since been recognized as a global regulator of RNA polymerase II (RNAPII) activity across the genome (PMID: 32355215). The complex associates with the C-terminal domain of RNAPII and is involved in the transcription of various RNA species, including messenger RNAs (mRNAs), enhancer RNAs (eRNAs), and long non-coding RNAs (lncRNAs) (PMID: 23931758). By modulating RNAPII pause-release and termination, the Integrator complex fine-tunes gene expression programs essential for development and cellular homeostasis (PMID: 30401431). Dysregulation of the complex is implicated in several human pathologies, including neurodevelopmental disorders like Galloway-Mowat syndrome and various cancers, such as leukemia and lung cancer, where it can drive oncogenic transcriptional programs (PMID: 29149601, PMID: 32355215). Consequently, the Integrator complex, particularly its catalytic subunit INTS11 which possesses endonuclease activity, is emerging as a potential therapeutic target for small-molecule inhibition in oncology (PMID: 32355215). Its role in viral transcription, particularly for HIV-1, also suggests potential applications in infectious disease (PMID: 25601755).

Other names

INT complexINTS complexRNA polymerase II subunit-associated complex

Endonuclease inhibition of the INTS11 subunit and disruption of RNA polymerase II transcriptional control (PMID: 32355215).