Analysis of U8 snoRNA Variants in Zebrafish Reveals How Bi-allelic Variants Cause Leukoencephalopathy with Calcifications and Cysts.

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

SUBMITTER: Badrock AP 

PROVIDER: S-EPMC7212298 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature