PUBLICATION
The Primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress–response pathway
- Authors
- Skarie, J.M., and Link, B.A.
- ID
- ZDB-PUB-080515-6
- Date
- 2008
- Source
- Human molecular genetics 17(16): 2474-2485 (Journal)
- Registered Authors
- Link, Brian, Skarie, Jonathan M.
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Nucleolus/metabolism
- Cytoplasm/metabolism
- Disease Models, Animal
- Gene Expression
- Glaucoma, Open-Angle/genetics
- Glaucoma, Open-Angle/metabolism*
- Glaucoma, Open-Angle/physiopathology*
- Humans
- Molecular Sequence Data
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism
- Protein Transport
- RNA Processing, Post-Transcriptional*
- RNA, Ribosomal
- RNA, Ribosomal, 18S/genetics*
- Saccharomyces cerevisiae/genetics
- Saccharomyces cerevisiae/metabolism
- Saccharomyces cerevisiae Proteins/genetics
- Saccharomyces cerevisiae Proteins/metabolism
- Signal Transduction*
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/analysis
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 18469340 Full text @ Hum. Mol. Genet.
Citation
Skarie, J.M., and Link, B.A. (2008) The Primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress–response pathway. Human molecular genetics. 17(16):2474-2485.
Abstract
Primary open angle glaucoma (POAG) is a genetically complex neuropathy that affects retinal ganglion cells and is a leading cause of blindness worldwide. WDR36, a gene of unknown function, was recently identified as causative for POAG at locus GLC1G. Subsequent studies found disease associated variants in control populations, leaving the role of WDR36 in this disease unclear. To address this issue we determined the function of WDR36. We studied Wdr36 in zebrafish and found it is the functional homolog of yeast Utp21. Utp21 is cell essential and functions in the nucleolar processing of 18S rRNA, which is required for ribosome biogenesis. Evidence for functional homology comes from sequence alignment, ubiquitous expression, sub-cellular localization to the nucleolus, and loss of function phenotypes that include defects in 18S rRNA processing and abnormal nucleolar morphology. Additionally, we show loss of Wdr36 function leads to an activation of the p53 stress response pathway, suggesting that co-inheritance of defects in p53-pathway genes may influence the impact of WDR36 variants on POAG. While these results overall do not provide evidence for or against a role of WDR3 6 in POAG, they do provide important baseline information for future studies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping