PXD010821-3

PXD010821 is an original dataset announced via ProteomeXchange.

Title	Splicing factor PRPF31 retinitis pigmentosa (RP11) is caused by disrupted alternative splicing programmes for genes implicated in pre-mRNA splicing, cellular adhesion and ciliogenesis
Description	Mutations in pre-mRNA processing factors (PRPFs) cause autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause retinal disease. We have generated 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.
HostingRepository	PRIDE
AnnounceDate	2018-12-04
AnnouncementXML	Submission_2018-12-04_03:58:55.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kuan-Ting Pan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-20 02:24:11	ID requested
1	2018-08-20 03:49:50	announced
2	2018-10-16 03:33:48	announced	Updated publication reference for PubMed record(s): 30315276.
⏵ 3	2018-12-04 03:58:57	announced	Updated project metadata.
4	2024-10-22 04:13:32	announced	2024-10-22: Updated project metadata.

Buskin A, Zhu L, Chichagova V, Basu B, Mozaffari-Jovin S, Dolan D, Droop A, Collin J, Bronstein R, Mehrotra S, Farkas M, Hilgen G, White K, Pan KT, Treumann A, Hallam D, Bialas K, Chung G, Mellough C, Ding Y, Krasnogor N, Przyborski S, Zwolinski S, Al-Aama J, Alharthi S, Xu Y, Wheway G, Szymanska K, McKibbin M, Inglehearn CF, Elliott DJ, Lindsay S, Ali RR, Steel DH, Armstrong L, Sernagor E, Urlaub H, Pierce E, L, ü, hrmann R, Grellscheid SN, Johnson CA, Lako M, Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat Commun, 9(1):4234(2018) [pubmed]

curator keyword: Biological

submitter keyword: RP11, iPSCs, pre-mRNA splicing, retinal organoids

Henning Urlaub
contact affiliation	Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry Department of Clinical Chemistry, University Medical Center Goettingen
contact email	henning.urlaub@mpibpc.mpg.de
lab head
Kuan-Ting Pan
contact affiliation	MPI for Biophysical Chemistry
contact email	kpan@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010821
     1. Label: PRIDE project
     2. Name: Splicing factor PRPF31 retinitis pigmentosa (RP11) is caused by disrupted alternative splicing programmes for genes implicated in pre-mRNA splicing, cellular adhesion and ciliogenesis