Avtor/Urednik		Eifler, Tristan T.; Shao, Wei; Bartholomeeusen, Koen; Fujinaga, Koh; Jäger, Stefanie; Johnson, Jeff R.; Luo, Zeping; Krogan, Nevan J.; Peterlin, Matija Boris
Naslov		Cyclin-dependent kinase 12 increases 3' end processing of growth factor-induced c-FOS transcripts
Tip		članek
Vol. in št.		Letnik 35, št. 2
Leto izdaje		2015
Obseg		str. 468-478
ISSN		0270-7306 - Molecular and cellular biology
Jezik		eng
Abstrakt		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.
Proste vsebinske oznake		cyclin-dependent kinase growth factor RNA polymerase ciklinsko odvisne kinaze rastni faktor RNA polimeraza