PXD055515

PXD055515 is an original dataset announced via ProteomeXchange.

Title	Molecular and cellular mechanisms driven by PABPN1 nuclear aggregates
Description	Disease-associated RNA binding protein (RBP) aggregation is a hallmark of several neurodegenerative disorders, contributing to their pathogenesis by disrupting cell homeostasis leading to cell dysfunction. In oculopharyngeal muscular dystrophy (OPMD), an expansion mutation in PABPN1 results in nuclear aggregates, but their role in disease mechanism and cellular dysfunction remains unclear. Using an inducible muscle cell model, we investigated PABPN1's effects on RNA and protein contents in nuclear, cytosolic, and insoluble fractions. We find that PABPN1 aggregates form fibrils similar to those in patients, and PABPN1 function is impaired as in the loss-of-function model. In cells expressing the pathogenic PABPN1, RBPs are enriched in the insoluble fraction, mRNA is sequestered in the nucleus, nuclear export is impaired, and translation efficiency decreases. Additionally, nuclear aggregates lead to reduced endogenous PABPN1 levels. We propose that PABPN1 aggregates and other disease-associated RBPs contribute to PABPN1 gain and loss-of-function, driving cell dysfunction in OPMD.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_16:30:43.033.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	methionine oxidation with neutral loss of 64 Da; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-03 05:58:15	ID requested
⏵ 1	2026-09-06 16:30:43	announced

Shademan M, Flannery S, Bos E, Evers TMJ, Sheikhhassani V, Mashaghi A, Kusters B, van Engelen B, Sharp TH, Fischer R, Kessler BM, Raz V, Nuclear Protein Aggregates Disrupt RNA Processing and Alter Biomechanics in a Muscle Cell Model of OPMD. Aging Dis, 17(5):2583-2603(2025) [pubmed]

10.14336/ad.2025.0699;

submitter keyword: Subcellular fractionation,oculopharyngeal muscular dystrophy

Roman Fischer
contact affiliation	Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
contact email	roman.fischer@ndm.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	Target Discovery Institute, NDMRB
contact email	iolanda.vendrell@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055515
     1. Label: PRIDE project
     2. Name: Molecular and cellular mechanisms driven by PABPN1 nuclear aggregates