Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase

Dephosphorylating RNA polymerase II Transcription in metazoans requires coordination of multiple factors to control the progression of polymerases and the integrity of their RNA products. Zheng et al. identified a new dual-enzyme complex called INTAC, which is composed of protein phosphatase 2A (PP2A) core enzyme and the multisubunit RNA endonuclease Integrator. Structural and functional studies show that INTAC functions as a noncanonical PP2A holoenzyme that dephosphorylates the C-terminal domain of RNA polymerase II to attenuate transcription. This study provides a direct connection between PP2A-mediated dephosphorylation and transcriptional regulation, two fundamental cellular processes. Science , this issue p. eabb5872