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The primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway. Hum Mol Genet 2008 Aug 15;17(16):2474-85

Date

05/13/2008

Pubmed ID

18469340

Pubmed Central ID

PMC2722886

DOI

10.1093/hmg/ddn147

Scopus ID

2-s2.0-48249142323   75 Citations

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 that 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. Although these results overall do not provide evidence for or against a role of WDR36 in POAG, they do provide important baseline information for future studies.

Author List

Skarie JM, Link BA

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Nucleolus
Cytoplasm
Disease Models, Animal
Gene Expression
Glaucoma, Open-Angle
Humans
Molecular Sequence Data
Nuclear Proteins
Protein Transport
RNA Processing, Post-Transcriptional
RNA, Ribosomal
RNA, Ribosomal, 18S
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Signal Transduction
Tumor Suppressor Protein p53
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0