CDK12 and Integrator-PP2A complex modulates LEO1 phosphorylation for processive transcription elongation

5Citations
Citations of this article
16Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Cyclin-dependent kinase 12 (CDK12) interacts with cyclin K to form a functional nuclear kinase that promotes processive transcription elongation through phosphorylation of the C-terminal domain of RNA polymerase II (Pol II). To gain a comprehensive understanding of CDK12's cellular function, we used chemical genetic and phosphoproteomic screening to identify a landscape of nuclear human CDK12 substrates, including regulators of transcription, chromatin organization, and RNA splicing. We further validated LEO1, a subunit of the polymerase- associated factor 1 complex (PAF1C), as a bona fide cellular substrate of CDK12. Acute depletion of LEO1, or substituting LEO1 phosphorylation sites with alanine, attenuated PAF1C association with elongating Pol II and impaired processive transcription elongation. Moreover, we discovered that LEO1 interacts with and is dephosphorylated by the Integrator-PP2A complex (INTAC) and that INTAC depletion promotes the association of PAF1C with Pol II. Together, this study reveals an uncharacterized role for CDK12 and INTAC in regulating LEO1 phosphorylation, providing important insights into gene transcription and its regulation.

Cite

CITATION STYLE

APA

Qiu, M., Yin, Z., Wang, H., Lei, L., Li, C., Cui, Y., … Liang, K. (2023). CDK12 and Integrator-PP2A complex modulates LEO1 phosphorylation for processive transcription elongation. Science Advances, 9(20). https://doi.org/10.1126/sciadv.adf8698

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free