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Cyclin-dependent kinase 12 increases 3' end processing of growth factor-induced c-FOS transcripts

Journal Contribution - Journal Article

Transcriptional cyclin-dependent kinases (CDKs) regulate RNA polymerase II initiation and elongation as well as cotranscriptional mRNA processing. In this report, we describe an important role for CDK12 in the epidermal growth factor (EGF)-induced c-FOS proto-oncogene expression in mammalian cells. This kinase was found in the exon junction complexes (EJC) together with SR proteins and was thus recruited to RNA polymerase II. In cells depleted of CDK12 or eukaryotic translation initiation factor 4A3 (eIF4A3) from the EJC, EGF induced fewer c-FOS transcripts. In these cells, phosphorylation of serines at position 2 in the C-terminal domain (CTD) of RNA polymerase II, as well as levels of cleavage-stimulating factor 64 (Cstf64) and 73-kDa subunit of cleavage and polyadenylation specificity factor (CPSF73), was reduced at the c-FOS gene. These effects impaired 3' end processing of c-FOS transcripts. Mutant CDK12 proteins lacking their Arg-Ser-rich (RS) domain or just the RS domain alone acted as dominant negative proteins. Thus, CDK12 plays an important role in cotranscriptional processing of c-FOS transcripts.

Journal: Curr Protoc Cell Biol
ISSN: 1934-2616
Issue: 2
Volume: 35
Pages: 468-78
Publication year:2015
Keywords:Cyclin-Dependent Kinases, Humans, Intercellular Signaling Peptides and Proteins, Mutation, Phosphorylation, Proto-Oncogene Proteins c-fos, RNA Polymerase II, RNA, Messenger, Transcriptional Activation