PXD035452 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Amyotrophic Lateral Sclerosis-associated Mutants of SOD1 Modulate miRNA Biogenesis through Aberrant Interactions with Exportin 5 |
Description | Mutations in SOD1 (Superoxide Dismutase 1) gene are associated with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. By employing ascorbate peroxidase (APEX)-based proximity labeling, coupled with LC-MS/MS analysis, we uncovered 37 and 28 proteins exhibiting higher abundance in the proximity proteomes of SOD1G85R and SOD1G93A, respectively, than that of the wild-type SOD1. Immunoprecipitation followed by western blot analysis confirmed the preferential binding of one of these proteins, exportin 5 (XPO5), toward the two mutants of SOD1 over its wild-type counterpart. In line with the established function of XPO5 in pre-miRNA transport, we observed diminished nucleocytoplasmic transport of pre-miRNAs in cells with ectopic expression of the two SOD1 mutants over those expressing the wild-type counterpart. On the other hand, RT-qPCR results revealed significant elevations in mature miRNA in cells expressing the two SOD1 mutants, which are attributed to diminished inhibitory effect of XPO5 on Dicer-mediated cleavage of pre-miRNA to mature miRNA. Together, our chemoproteomic approach led to the revelation of a novel mechanism through which ALS-associated mutants of SOD1 perturb miRNA biogenesis, i.e., through aberrant binding toward XPO5. |
HostingRepository | PRIDE |
AnnounceDate | 2024-01-26 |
AnnouncementXML | Submission_2024-01-26_06:29:11.336.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Xingyuan Chen |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-07-20 04:54:16 | ID requested | |
⏵ 1 | 2024-01-26 06:29:12 | announced | |
Publication List
10.1021/acschembio.2c00591; |
Chen X, He X, Yang YY, Wang Y, Amyotrophic Lateral Sclerosis-Associated Mutants of SOD1 Modulate miRNA Biogenesis through Aberrant Interactions with Exportin 5. ACS Chem Biol, 17(12):3450-3457(2022) [pubmed] |
Keyword List
submitter keyword: LC-MS Affinity Purification SOD1 APEX |
Contact List
YINSHENG WANG |
contact affiliation | UNIVERSITY OF CALIFORNIA-RIVERSIDE |
contact email | yinsheng@ucr.edu |
lab head | |
Xingyuan Chen |
contact affiliation | University of California, Riverside |
contact email | xchen339@ucr.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035452
- Label: PRIDE project
- Name: Amyotrophic Lateral Sclerosis-associated Mutants of SOD1 Modulate miRNA Biogenesis through Aberrant Interactions with Exportin 5