PXD071251

PXD071251 is an original dataset announced via ProteomeXchange.

Title	Targeted antisense oligonucleotide therapy rescues PRPF31 expression in retinitis pigmentosa caused by a splicing mutation
Description	Pathogenic variants in splicing factors are the second most common cause of autosomal dominant retinitis pigmentosa (RP), with mutations in PRPF31 being the most prevalent. Here, we characterize a novel intronic variant in PRPF31 (c.1074-11C>G) that creates a cryptic 3′ splice site, resulting in an aberrantly spliced transcript predicted to encode a protein with an altered C-terminus. However, the pathogenic protein was not detected in patient-derived induced pluripotent stem cells (iPSCs). In addition, expression of PRPF31 protein was reduced in patient iPSC-derived retinal pigment epithelium (RPE). To correct the splicing defect, we designed a panel of antisense oligonucleotides (ASOs) targeting putative RNA-binding sites in exon 10 and intron 10 and identified a candidate that corrects PRPF31 splicing in a minigene reporter system as well as in patient-derived iPSCs and RPE. Finally, we showed that ASO treatment enhances PRPF31 protein expression in patient iPSC-derived RPE, supporting its potential as a therapeutic approach to restore PRPF31 expression in RP patients.
HostingRepository	PRIDE
AnnounceDate	2026-06-12
AnnouncementXML	Submission_2026-06-12_05:11:47.934.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marek Vrbacky
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-25 23:45:35	ID requested
⏵ 1	2026-06-12 05:11:48	announced

10.1016/J.YMTHE.2026.05.033;

submitter keyword: PRPF31, cryptic splice site, ASO treatment,Retinitis pigmentosa, aberrant splicing

David Stanek
contact affiliation	Laboratory of RNA Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague, Czechia
contact email	stanek@img.cas.cz
lab head
Marek Vrbacky
contact affiliation	Czech Academy of Sciences
contact email	proteom.krc@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD071251

PRIDE project URI

• PRIDE
  1. PXD071251
     1. Label: PRIDE project
     2. Name: Targeted antisense oligonucleotide therapy rescues PRPF31 expression in retinitis pigmentosa caused by a splicing mutation