CDK12 and CDK13 are C-terminal domain (CTD) serine kinases that phosphorylate Ser2 in the CTD of RNA polymerase II and which regulate co-transcriptional processing, including splicing and 3'-end RNA processing [1,3-4,6]. Although CDK12 and CDK13 are closely related structurally, they differ in function. Whilst CDK12 is essential for the expression of genes that are involved in the DNA damage response pathway [2] (generally longer genes with a high number of exons), CDK13 activity affects genes that are required for protein translation.

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3. Davidson L, Muniz L, West S. (2014) 3' end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells. Genes Dev, 28 (4): 342-56. [PMID:24478330]

4. Eifler TT, Shao W, Bartholomeeusen K, Fujinaga K, Jäger S, Johnson JR, Luo Z, Krogan NJ, Peterlin BM. (2015) Cyclin-dependent kinase 12 increases 3' end processing of growth factor-induced c-FOS transcripts. Mol Cell Biol, 35 (2): 468-78. [PMID:25384976]

5. Ito M, Tanaka T, Toita A, Uchiyama N, Kokubo H, Morishita N, Klein MG, Zou H, Murakami M, Kondo M et al.. (2018) Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors. J Med Chem, 61 (17): 7710-7728. [PMID:30067358]

6. Kohoutek J, Blazek D. (2012) Cyclin K goes with Cdk12 and Cdk13. Cell Div, 7: 12. [PMID:22512864]

7. Yang J, Chang Y, Zhou K, Huang W, Tien JC, Zhang P, Liu W, Zhou L, Zhou Y, Ren X et al.. (2025) Discovery of YJZ5118: A Potent and Highly Selective Irreversible CDK12/13 Inhibitor with Synergistic Effects in Combination with Akt Inhibition. J Med Chem, 68 (6): 6718-6734. [PMID:40080446]