A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation

Abstract

Controlled gene expression is achieved through the intricate regulation of RNA polymerase II (Pol II) progression through transcription-cycle checkpoints. While the contribution of CDK9 for Pol II pause-release is well established, the requirement for other cyclin-dependent kinases (CDKs) has not been fully elucidated. In this study, we propose a critical role for CDK11 in the Pol II pausing-to-elongation transition at a checkpoint that precedes and is independent from CDK9. Selective CDK11 inhibition or degradation results in acute ablation of RNA synthesis near the beginning of transcriptional units and genome-wide stalling of Pol II at transcription start site (TSS)-proximal regions. High..