PXD055515 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| 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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2024-09-03 05:58:15 | ID requested | |
| ⏵ 1 | 2026-09-06 16:30:43 | announced | |
Publication List
| 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; |
Keyword List
| submitter keyword: Subcellular fractionation,oculopharyngeal muscular dystrophy |
Contact List
| 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 | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD055515
- Label: PRIDE project
- Name: Molecular and cellular mechanisms driven by PABPN1 nuclear aggregates
