PXD056515-1

PXD056515 is an original dataset announced via ProteomeXchange.

Title	Unraveling the impact of VHL Exon 2 mutations identified in Erythrocytosis or von Hippel-Lindau disease, identified hnRNP F and hnRNP AB as new RNA-Binding Proteins involved in VHL splicing.
Description	This study explores the impact of mutations in the exon 2 of the von Hippel-Lindau (VHL) gene, associated with erythrocytosis or von Hippel-Lindau disease. We analyzed 15 genetic variants, including missense and synonymous mutations, to assess their effects on VHL protein stability and splicing. Using in silico predictions and functional assays, we found that specific mutations reduce protein stability, induce exon skipping and can cause a shift in the splice donor site. This study highlighted new exonic splicing regulatory regions. Notably, by performing RNA-protein pull down we identified two novel RNA-binding proteins, hnRNP F and hnRNP AB, as key regulators of VHL splicing. Our findings reveal the limitations of current splicing prediction tools in recognizing exonic splicing enhancer (ESE) or silencer (ESS) sequences and suggest that mutations can differentially affect disease phenotypes by influencing both protein stability and splicing. These insights enhance our understanding of the molecular mechanisms underlying VHL-associated disorders, delimitate new regulatory regions and demonstrates the role of new RNA-binding proteins in VHL splicing regulation.
HostingRepository	PRIDE
AnnounceDate	2025-09-25
AnnouncementXML	Submission_2025-09-25_09:50:06.826.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marjorie Leduc
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-04 13:25:57	ID requested
⏵ 1	2025-09-25 09:50:07	announced

10.1016/J.AJHG.2025.09.002;

submitter keyword: DIA, RNA-Binding Proteins,von Hippel-Lindau disease, Erythrocytosis

Betty Gardie
contact affiliation	1 Ecole Pratique des Hautes Etudes, EPHE, Université Paris Sciences et Lettres, Paris, France, 2 Nantes Université, CNRS, INSERM, l'Institut du Thorax, F-44000 Nantes, France, 3 Laboratoire d’Excellence GR-Ex, Paris, France, 75010
contact email	betty.gardie@univ-nantes.fr
lab head
Marjorie Leduc
contact affiliation	Plateforme protéomique 3P5, Université de Paris, Institut Cochin, INSERM, CNRS,
contact email	marjorie.leduc@inserm.fr
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/2025/09/PXD056515

PRIDE project URI

• PRIDE
  1. PXD056515
     1. Label: PRIDE project
     2. Name: Unraveling the impact of VHL Exon 2 mutations identified in Erythrocytosis or von Hippel-Lindau disease, identified hnRNP F and hnRNP AB as new RNA-Binding Proteins involved in VHL splicing.