PXD035452

PXD035452 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 04:54:16	ID requested
⏵ 1	2024-01-26 06:29:12	announced

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]

submitter keyword: LC-MS Affinity Purification SOD1 APEX

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD035452

PRIDE project URI

• PRIDE
  1. PXD035452
     1. Label: PRIDE project
     2. Name: Amyotrophic Lateral Sclerosis-associated Mutants of SOD1 Modulate miRNA Biogenesis through Aberrant Interactions with Exportin 5