Interaction of cyclin-dependent kinase 12/CrkRS with cyclin K1 is required for the phosphorylation of the C-terminal domain of RNA polymerase II.
| Authors | Cheng SW, Kuzyk MA, Moradian A, Ichu TA, Chang VC, Tien JF, Vollett SE, Griffith M, Marra MA & Morin GB. |
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| Abstract | CrkRS (Cdc2-related kinase, Arg/Ser), or CDK12 (Cyclin Dependent Kinase 12), is a serine/threonine kinase believed to coordinate transcription and RNA splicing. While CDK12/CrkRS complexes were known to phosphorylate the C-Terminal Domain (CTD) of RNA Pol II, the cyclin regulating this activity was not known. Using immunoprecipitation and mass spectrometry, we identified a 65 KDa isoform of CYCLIN K (K1) in endogenous CDK12/CrkRS protein complexes. We show that CYCLIN K1 complexes isolated from mammalian cells contain CDK12/CrkRS but do not contain CDK9, a presumed partner of CYCLIN K. Analysis of extensive RNA-seq data shows that the 65 KDa CYCLIN K1 isoform is the predominantly expressed form across numerous tissue types. We also demonstrate that CDK12/CrkRS is dependent on CYCLIN K1 for its kinase activity and siRNA knockdown of CDK12/CrkRS or CYCLIN K1 have similar affects on the expression of a luciferase reporter gene. Our data suggest that CYCLIN K1 is the primary cyclin partner for CDK12/CrkRS and CYCLIN K1 is required to activate CDK12/CrkRS to phosphorylate the CTD of RNA Pol II. These properties are consistent with a role of CDK12/CrkRS in regulating gene expression through phosphorylation of RNA Pol II. |
| Journal Name and Citation | Mol Cell Biol. 2012 Nov;32(22):4691-704. |
| Date of Publication | 2012/11/01 |
| Publication Link | http://mcb.asm.org/content/32/22/4691.abstract91.abstract |