CDK11 activates CDK12 to trigger the elongation of RNA Polymerase II.

CDK11 is an essential cyclin-dependent kinase in higher eukaryotes, yet its specific substrates and functional roles have remained elusive. Our findings reveal that CDK11 is functionally analogous to the yeast Bur1 kinase, phosphorylating the repeat region of hSpt5 and the linker domain of Rpb1 in RNA Polymerase II (Pol II). Inhibition of CDK11 results in a significant reduction of active Pol II not only at transcription start sites but also along gene bodies. Further investigation finds that CDK11 is crucial for the phosphorylation and activation of CDK12, which is essential for the elongation of Pol II. Moreover, we find that CDK10 can partially compensate for the function of CDK11. Combining with earlier functional elucidation of CDK9 from us, the consequent roles of CDK7/8, CDK9, CDK10/11, and CDK12/13 in transcription regulation in metazoans are established.