CDK11 complexes promote pre-mRNA splicing

The PITSLRE protein kinases, hereafter referred to as CDK11 because of their association with the cyclin L regulatory partner, belong to large molecular weight protein complexes that contain RNA polymerase II. These CDK11^p110 complexes have been reported to influence transcription as well as interact with the general pre-mRNA-splicing factor RNPS1. Some of these complexes may also play a role in pre-mRNA splicing. Using a two-hybrid interactive screen, the splicing protein 9G8 was identified as an in vivo partner for CDK11^p110. The identification of several splicing-related factors as CDK11^p110 interactors along with the close relationship between transcription and splicing indicated that CDK11^p110 might influence splicing activity directly. Immunodepletion of CDK11^p110 from splicing extracts greatly reduced the appearance of spliced products using an in vitro assay system. Moreover, the re-addition of these CDK11^p110 immune complexes to the CDK11^p110-immunodepleted splicing reactions completely restored splicing activity. Similarly, the addition of purified CDK11^p110 amino-terminal domain protein was sufficient to inhibit the splicing reaction. Finally, 9G8 is a phosphoprotein in vivo and is a substrate for CDK11^p110 phosphorylation in vitro. These data are among the first demonstrations showing that a CDK activity is functionally coupled to the regulation of pre-mRNA-splicing events and further support the hypothesis that CDK11^p110 is in a signaling pathway that may help to coordinate transcription and RNA-processing events.