PITSLRE p110 protein kinases associate with transcription complexes and affect their activity.

Although the PITSLRE protein kinases are members of the cyclin-dependent kinase superfamily, their cellular function is unclear. Previously we demonstrated that the general RNA splicing factor RNPS1 is a specific PITSLRE p110 kinase interactor in vivo. This suggests that the PITSLRE family of protein kinases is involved in some aspect of RNA processing or transcription. Here we identify multiple transcriptional elongation factors, including ELL2, TFIIF(1), TFIIS, and FACT, as PITSLRE kinase-associated proteins. We demonstrate that PITSLRE p110 protein kinases co-immunoprecipitate and/or co-purify with these elongation factors as well as with RNA polymerase II. Antibody-mediated inhibition of PITSLRE kinase specifically suppressed RNA polymerase II-dependent in vitro transcription initiated at a GC-rich (adenosine deaminase) or TATA box-dependent (Ad2ML) promoter, and this suppression was rescued by readdition of purified PITSLRE p110 kinase. Together, these data strongly suggest that PITSLRE protein kinases participate in a signaling pathway that potentially regulates or links transcription and RNA processing events.