Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium CDK8 and CDK19 form a conserved cyclin-dependent kinase subfamily that interacts with the essential transcription complex, Mediator, and also promotes transcription by phosphorylating the C-terminal domain (CTD) of RNA polymerase II. Cells lacking either CDK8 or CDK19 are viable and have limited transcriptional alterations, but whether the two kinases redundantly control cell differentiation is unknown. Here, we find that CDK8 is dispensable for RNA polII CTD phosphorylation, regulation of gene expression, normal intestinal homeostasis and efficient tumourigenesis in mice. Furthermore, CDK8 is largely redundant with CDK19 in the control of gene expression. Yet, while their combined deletion in intestinal organoids reduces long-term proliferative capacity, it is not lethal and allows differentiation. Nevertheless, in double mutant organoids, the cystic fibrosis transmembrane conductance regulator (CFTR) pathway is transcriptionally and functionally downregulated, leading to mucus accumulation and increased secretion by goblet cells. This phenotype can be recapitulated by pharmacological inhibition of CDK8/19 kinase activity. Thus, the Mediator kinases are not essential for cell proliferation and differentiation, but they cooperate to regulate tissue-specific transcriptional programmes.
20
The categories of this paper are: pharmacology
16
The categories of this paper are: microbiology
4
The categories of this paper are: neuroscience
8
The categories of this paper are: genomics
26
The categories of this paper are: biochemistry
28
The categories of this paper are: communication
29
The categories of this paper are: education
31
The categories of this paper are: paleontology
0
The categories of this paper are: genetics
13
The categories of this paper are: animal
7
The categories of this paper are: ecology
32
The categories of this paper are: zoology
9
The categories of this paper are: synthetic
21
The categories of this paper are: toxicology
12
The categories of this paper are: behavior
3
The categories of this paper are: evolutionary