PXD070093 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | NSUN1-m5C is linked to TDP-43 neurotoxicity |
| Description | In amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the nuclear RNA-binding protein TDP-43 mislocalises to the cytoplasm and forms insoluble aggregates, but the mechanisms controlling this remain unclear. We define a native TDP-43 interactome in human SH-SY5Y cells and identify proteins linked to the 5-methylcytosine (m5C) RNA modification as highly enriched. Using a Drosophila model of TDP-43 pathology, we show that aberrant activity of m5C-RNA methyltransferases Nsun1 drives TDP-43-induced m5C-RNA hypermethylation, while Nsun1 downregulation alleviates TDP-43–induced degeneration, lifespan deficits, and cytoplasmic accumulation. In human cells, TDP-43 selectively interacts with NSUN1 isoform 3 independently of RNA. Furthermore, NSUN1 is nucleolar and TDP-43 is largely nucleoplasmic, yet they interact in both compartments, suggesting functional roles beyond their predominant localisations. In ALS/FTD post-mortem frontal cortex, NSUN1 isoform 3 persists, while the shorter isoform is reduced, suggesting that a pool of NSUN1 capable of contributing to pathological TDP-43 interactions remains in disease. These findings suggest that TDP-43 neurotoxicity is coupled to NSUN1 activation and m5C-RNA methylation, revealing a potential therapeutic axis in ALS/FTD. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-11-03 |
| AnnouncementXML | Submission_2025-11-03_03:22:18.412.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Leeanne McGurk |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-10-30 05:49:08 | ID requested | |
| ⏵ 1 | 2025-11-03 03:22:18 | announced | |
Publication List
Keyword List
| submitter keyword: NOP2, rRNA,Drosophila, nucleolus, neurodegenerative |
Contact List
| Leeanne McGurk |
|---|
| contact affiliation | Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK |
| contact email | LMcgurk001@dundee.ac.uk |
| lab head | |
| Leeanne McGurk |
|---|
| contact affiliation | University of Dundee |
| contact email | lmcgurk001@dundee.ac.uk |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD070093
- Label: PRIDE project
- Name: NSUN1-m5C is linked to TDP-43 neurotoxicity
