@article {1347429,
	title = {Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa},
	journal = {Nat Commun},
	volume = {9},
	number = {1},
	year = {2018},
	month = {2018 Oct 12},
	pages = {4234},
	abstract = {Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause non-syndromic retinal disease. Here, we generate transcriptome profiles from RP11 (PRPF31-mutated) patient-derived retinal organoids and retinal pigment epithelium (RPE), as well as Prpf31 mouse tissues, which revealed that disrupted alternative splicing occurred for specific splicing programmes. Mis-splicing of genes encoding pre-mRNA splicing proteins was limited to patient-specific retinal cells and Prpf31 mouse retinae and RPE. Mis-splicing of genes implicated in ciliogenesis and cellular adhesion was associated with severe RPE defects that include disrupted apical - basal polarity, reduced trans-epithelial resistance and phagocytic capacity, and decreased cilia length and incidence. Disrupted cilia morphology also occurred in patient-derived photoreceptors, associated with progressive degeneration and cellular stress. In situ gene editing of a pathogenic mutation rescued protein expression and key cellular phenotypes in RPE and photoreceptors, providing proof of concept for future therapeutic strategies.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-06448-y},
	author = {Buskin, Adriana and Zhu, Lili and Chichagova, Valeria and Basu, Basudha and Mozaffari-Jovin, Sina and Dolan, David and Droop, Alastair and Collin, Joseph and Bronstein, Revital and Mehrotra, Sudeep and Farkas, Michael and Hilgen, Gerrit and White, Kathryn and Pan, Kuan-Ting and Treumann, Achim and Hallam, Dean and Bialas, Katarzyna and Chung, Git and Mellough, Carla and Ding, Yuchun and Krasnogor, Natalio and Przyborski, Stefan and Zwolinski, Simon and Al-Aama, Jumana and Alharthi, Sameer and Xu, Yaobo and Wheway, Gabrielle and Szymanska, Katarzyna and McKibbin, Martin and Inglehearn, Chris F and Elliott, David J and Lindsay, Susan and Ali, Robin R and Steel, David H and Armstrong, Lyle and Sernagor, Evelyne and Urlaub, Henning and Pierce, Eric and L{\"u}hrmann, Reinhard and Grellscheid, Sushma-Nagaraja and Johnson, Colin A and Lako, Majlinda}
}
