biostudies-literatureGeorgiou MEuropean Research CouncilFight for SightRetina UKNIMADNational Institute for Medical Research DevelopmentMRC UKe759https://www.ebi.ac.uk/biostudies/studies/S-EPMC8926896biostudies-literatureUnknown12(3)<h4>Introduction</h4>Mutations in pre-mRNA processing factor 31 (PRPF31), a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations in ubiquitously expressed tri-snRNP proteins result in retina-specific disorders, and so far, the underlying mechanism of splicing factors-related RP is poorly understood.<h4>Methods</h4>We used the induced pluripotent stem cell (iPSC) technology to generate retinal organoids and RPE models from four patients with severe and very severe PRPF31-adRP, unaffected individuals and a CRISPR/Cas9 isogenic control.<h4>Results</h4>To fully assess the impacts of PRPF31 mutations, quantitative proteomics analyses of retinal organoids and RPE cells were carried out showing RNA spliciClinical and translational medicineActivation of autophagy reverses progressive and deleterious protein aggregation in PRPF31 patient-induced pluripotent stem cell-derived retinal pigment epithelium cells.PMC89268961456/1457CoG_614620GR584GR595614620MR/T017503/1989278Pan KTArmstrong LUrlaub HLudwig SEJLuhrmann RBuskin AKorolchuk VCollin JAl-Aama JYang CJohnson CAMolina MMNagaraja-Grellscheid SGeorgiou MAtkinson RAli RGoertler FMozaffari-Jovin SDavey TLako MfalseActivation of autophagy reverses progressive and deleterious protein aggregation in PRPF31 patient-induced pluripotent stem cell-derived retinal pigment epithelium cells.<h4>Introduction</h4>Mutations in pre-mRNA processing factor 31 (PRPF31), a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations in ubiquitously expressed tri-snRNP proteins result in retina-specific disorders, and so far, the underlying mechanism of splicing factors-related RP is poorly understood.<h4>Methods</h4>We used the induced pluripotent stem cell (iPSC) technology to generate retinal organoids and RPE models from four patients with severe and very severe PRPF31-adRP, unaffected individuals and a CRISPR/Cas9 isogenic control.<h4>Results</h4>To fully assess the impacts of PRPF31 mutations, quantitative proteomics analyses of retinal organoids and RPE cells were carried out showing RNA splici2022-01-01T00:00:00Z2022 Mar2025-04-04T23:33:46.31Z2025-04-04T23:33:46.31ZS-EPMC89268963529755510.1002/ctm2.759