biostudies-literatureNazlamova LNIHR BioResourceNational Institute for Health Research (NIHR)Sight Research UKWellcome TrustAcademy of Medical Sciences1009430https://www.ebi.ac.uk/biostudies/studies/S-EPMC9513239biostudies-literatureUnknown13Retinitis pigmentosa (RP) is the most common cause of hereditary blindness, and may occur in isolation as a non-syndromic condition or alongside other features in a syndromic presentation. Biallelic or monoallelic mutations in one of eight genes encoding pre-mRNA splicing factors are associated with non-syndromic RP. The molecular mechanism of disease remains incompletely understood, limiting opportunities for targeted treatment. Here we use CRISPR and base edited <i>PRPF6</i> and <i>PRPF31</i> mutant cell lines, and publicly-available data from human <i>PRPF31</i> ^<i>+/-</i> patient derived retinal organoids and <i>PRPF31</i> siRNA-treated organotypic retinal cultures to confirm an enrichment of differential splicing of microtubule, centrosomal, cilium and DNA damage response pFrontiers in geneticsMicrotubule modification defects underlie cilium degeneration in cell models of retinitis pigmentosa associated with pre-mRNA splicing factor mutations.PMC9513239SBF004\1038RP-2016-07-011204378/Z/16/ZWheway GKarthik VLakowski JNazlamova LVilla Vasquez SSCheung MKLord JfalseMicrotubule modification defects underlie cilium degeneration in cell models of retinitis pigmentosa associated with pre-mRNA splicing factor mutations.Retinitis pigmentosa (RP) is the most common cause of hereditary blindness, and may occur in isolation as a non-syndromic condition or alongside other features in a syndromic presentation. Biallelic or monoallelic mutations in one of eight genes encoding pre-mRNA splicing factors are associated with non-syndromic RP. The molecular mechanism of disease remains incompletely understood, limiting opportunities for targeted treatment. Here we use CRISPR and base edited <i>PRPF6</i> and <i>PRPF31</i> mutant cell lines, and publicly-available data from human <i>PRPF31</i> ^<i>+/-</i> patient derived retinal organoids and <i>PRPF31</i> siRNA-treated organotypic retinal cultures to confirm an enrichment of differential splicing of microtubule, centrosomal, cilium and DNA damage response p2022-01-01T00:00:00Z20222026-05-08T03:12:39.119Z2025-02-19T00:34:59.255ZS-EPMC95132393617630010.3389/fgene.2022.1009430