CDK11 facilitates centromeric transcription to maintain centromeric cohesion during mitosis.

Abstract

Actively-transcribing RNA polymerase (RNAP)II is remained on centromeres to maintain centromeric cohesion during mitosis, although it is largely released from chromosome arms. This pool of RNAPII plays an important role in centromere functions. However, the mechanism of RNAPII retention on mitotic centromeres is poorly understood. We here demonstrate that Cyclin-dependent kinase (Cdk)11 is involved in RNAPII regulation on mitotic centromeres. Consistently, we show that Cdk11 knockdown induces centromeric cohesion defects and decreases Bub1 on kinetochores, but the centromeric cohesion defects are partially attributed to Bub1. Furthermore, Cdk11 knockdown and the expression of its kinase-dead version significantly reduce both RNAPII and elongating RNAPII (pSer2) levels on centromeres and decrease centromeric transcription. Importantly, the overexpression of centromeric α-satellite RNAs fully rescues Cdk11-knockdown defects. These results suggest that the maintenance of centromeric cohesion requires Cdk11-facilitated centromeric transcription. Mechanistically, Cdk11 localizes on centromeres where it binds and phosphorylates RNAPII to promote transcription. Remarkably, mitosis-specific degradation of G2/M Cdk11-p58 recapitulates Cdk11-knockdown defects. Altogether, our findings establish Cdk11 as an important regulator of centromeric transcription and as part of the mechanism for retaining RNAPII on centromeres during mitosis.