title: The primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway.
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.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Skarie
authors.forename: Brian A
authors.initials: BA
authors.lastname: Link
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D005902:Glaucoma, Open-Angle / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal; D012337:RNA, Ribosomal, 18S / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D012337:RNA, Ribosomal, 18S; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53; C531337:Utp21 protein, S cerevisiae; D029961:Zebrafish Proteins