Journal article

A PP2A-Integrator complex fine-tunes transcription by opposing CDK9

Stephin Vervoort, Sarah Welsh, Jennifer Devlin, Elisa Barbieri, Deborah Knight, Matteo Costacurta, Izabela Todorovski, Conor Kearney, Jarrod Sandow, Stefan Bjelosevic, Zheng Fan, Joep Vissers, Karolina Pavic, Ben Martin, Gareth Gregory, Isabella Kong, Edwin Hawkins, Simon Hogg, Madison Kelly, Andrea Newbold Show all

Published : 2020

Abstract

SUMMARY Gene expression is tightly controlled by Cyclin-dependent kinases (CDKs) which regulate the RNA Polymerase II (RNAPII) transcription cycle at discrete checkpoints. RNAPII pausing is a CDK9-controlled rate-limiting process that occurs shortly after initiation and is required for spatio-temporal control of transcription in multicellular organisms. We discovered that CDK9-mediated RNAPII pause-release is functionally opposed by a protein phosphatase 2A (PP2A) complex. PP2A dynamically competes for key CDK9 substrates, DSIF and RNAPII, and is recruited to transcription pausing sites by INTS6, a subunit of the Integrator complex. INTS6 depletion disrupts the Integrator-PP2A association an..

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