PXD050785

PXD050785 is an original dataset announced via ProteomeXchange.

Title	Amyotrophic Lateral Sclerosis-Associated Mutants of SOD1 Perturb mRNA Splicing through Aberrant Interactions with SRSF2
Description	Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that impacts neurons in the brain and spinal cord. Although a substantial number of studies have been conducted, much remains to be learned about the cellular mechanisms underlying ALS. In this study, we employed an engineered ascorbate peroxidase (APEX)-based proximity biotinylation, together with affinity pull-down of the ensuing biotinylated peptides, to investigate the proximity proteomes of human SOD1 and its two ALS-linked mutants, G85R and G93A. We were able to identify 25 common proteins with preferential enrichment in the proximity proteomes of SOD1G85R and SOD1G93A over wild-type SOD1. Our co-immunoprecipitation and Western blot analyses showed stronger binding of the two SOD1 mutants toward one of these proteins, SRSF2, than the wild-type counterpart. We also observed aberrant RNA splicing of three neurodegeneration-associated and SRSF2-regulated genes, including EIF4A2, SETX, and MELK, in cells with ectopic expression of the two SOD1 mutants relative to cells expressing the wild-type protein. The differences in splicing elicited by the SOD1 variants were markedly attenuated upon knockdown of SRSF2. Collectively, we uncovered that ALS-liked SOD1G85R and SOD1G93A mutants interact more strongly with SRSF2, and the aberrant interactions perturbed mRNA splicing. Thus, our work offered novel mechanistic insights into the contribution of the ALS-linked SOD1 mutants to disease etiology.
HostingRepository	PRIDE
AnnounceDate	2025-06-16
AnnouncementXML	Submission_2025-06-15_16:07:34.348.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xingyuan Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-19 18:15:15	ID requested
⏵ 1	2025-06-15 16:07:36	announced

10.1021/acs.analchem.4c01770;

Chen X, Cao Z, Wang Y, Amyotrophic Lateral Sclerosis-Associated Mutants of SOD1 Perturb mRNA Splicing through Aberrant Interactions with SRSF2. Anal Chem, 96(23):9713-9720(2024) [pubmed]

submitter keyword: SOD1, ALS, Affinity pulldown,LC-MSMS

Xingyuan Chen
contact affiliation	University of California, Riverside
contact email	xchen339@ucr.edu
lab head
Xingyuan Chen
contact affiliation	University of California, Riverside
contact email	xchen339@ucr.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050785
     1. Label: PRIDE project
     2. Name: Amyotrophic Lateral Sclerosis-Associated Mutants of SOD1 Perturb mRNA Splicing through Aberrant Interactions with SRSF2