ArticleAmerican journal of human genetics2020
Analysis of U8 snoRNA Variants in Zebrafish Reveals How Bi-allelic Variants Cause Leukoencephalopathy with Calcifications and Cysts.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 31 citations in OpenAlex.
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- PRICE: direct and robust detection of microRNAs at single-nucleotide resolution.Nature communications · 2026Article
- Systematic mapping of small nucleolar RNA interactions in human cells.RNA biology · 2025Article
- The 3'-5' exoribonuclease ISG20L2 contributes to 3' terminus maturation of 18S and 28S ribosomal RNAs.Nucleic acids research · 2025Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- The zebrafish (NAR genomics and bioinformatics · 2025Article
- Leukoencephalopathy, brain calcifications, and cysts (LCC): Two unique cases.Rare (Amsterdam, Netherlands) · 2025Article
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- Expanding the Natural History ofGenes · 2023Review
- In phase with the nucleolus.Cell research · 2023Article
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- Leukoencephalopathy, calcifications, and cysts: Labrune syndrome.Radiology case reports · 2023Article
- Characterization of a mutantFrontiers in immunology · 2023Article
- Antisense pairing and SNORD13 structure guide RNA cytidine acetylation.RNA (New York, N.Y.) · 2022Article
- Global mapping of RNA homodimers in living cells.Genome research · 2022Article
- Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease.BMC neurology · 2022Article
- U8 variants on the brain: a small nucleolar RNA and human disease.RNA biology · 2022Review
- The role of OncoSnoRNAs and Ribosomal RNA 2'-O-methylation in Cancer.RNA biology · 2021Review
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How mutations in the non-coding U8 snoRNA cause the neurological disorder leukoencephalopathy with calcifications and cysts (LCC) is poorly understood. Here, we report the generation of a mutant U8 animal model for interrogating LCC-associated pathology. Mutant U8 zebrafish exhibit defective central nervous system development, a disturbance of ribosomal RNA (rRNA) biogenesis and tp53 activation, which monitors ribosome biogenesis. Further, we demonstrate that fibroblasts from individuals with LCC are defective in rRNA processing. Human precursor-U8 (pre-U8) containing a 3' extension rescued mutant U8 zebrafish, and this result indicates conserved biological function. Analysis of LCC-associated U8 mutations in zebrafish revealed that one null and one functional allele contribute to LCC. We show that mutations in three nucleotides at the 5' end of pre-U8 alter the processing of the 3' extension, and we identify a previously unknown base-pairing interaction between the 5' end and the 3' extension of human pre-U8. Indeed, LCC-associated mutations in any one of seven nucleotides in the 5' end and 3' extension alter the processing of pre-U8, and these mutations are present on a single allele in almost all individuals with LCC identified to date. Given genetic data indicating that bi-allelic null U8 alleles are likely incompatible with human development, and that LCC is not caused by haploinsufficiency, the identification of hypomorphic misprocessing mutations that mediate viable embryogenesis furthers our understanding of LCC molecular pathology and cerebral vascular homeostasis.
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