ZCRB1

Cilia effects upon perturbation of ZCRB1

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-3.11) PMID:29459680

Phenotypes

Mouse phenotype:

preweaning lethality, incomplete penetrance, abnormal cornea morphology, abnormal vocalization, abnormal behavior, abnormal spleen morphology

Subcellular localization

cilia associated gene

Functional category

• Ciliary assembly/disassembly
• Viral interactions

Function

Human cell lines with a partial reduction in ZCRB1 expression exhibit significant dysregulation of the splicing and expression of U12-type genes, primarily due to dysregulation of U12 mono-snRNA. RNA-Seq and targeted analyses of minor intron-containing genes indicate a downregulation in the expression of genes involved in ciliogenesis, and consequentially an upregulation in WNT signaling. Additionally, zcrb1 CRISPR-Cas12a knockdown in zebrafish embryos led to gross developmental and body axis abnormalities, disrupted ciliogenesis, and upregulated WNT signaling, complementing our human cell studies. ZCRB1 protein has specifically role in cellular and developmental processes across species, shedding light on the multifaceted relationship between splicing regulation, ciliogenesis, and WNT signaling(PMID: 39149385).

Model organism evidence