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

Tristan T Eifler, Wei Shao, Koen Bartholomeeusen, Koh Fujinaga, Stefanie Jäger, Jeff R Johnson, Zeping Luo, Nevan J Krogan, B Matija Peterlin

Research output: Contribution to journalA2: International peer reviewed article (not A1-type)

Abstract

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.

Original languageEnglish
JournalCurrent Protocols in Cell Biology
Volume35
Issue number2
Pages (from-to)468-78
Number of pages11
ISSN1934-2616
DOIs
Publication statusPublished - Jan-2015
Externally publishedYes

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