PXD051918-1

PXD051918 is an original dataset announced via ProteomeXchange.

Title	An alternative cytoplasmic SFPQ isoform with divergent phase separation potential is upregulated in ALS
Description	Splicing factor proline- and glutamine-rich (SFPQ) is an RNA-binding protein that broadly regulates RNA metabolism. Although its nuclear roles are well-studied, evidence of SFPQ’s cytoplasmic functionality is emerging. Altered expression and nuclear-to-cytoplasmic mislocalisation of SFPQ is a hallmark of amyotrophic lateral sclerosis (ALS), yet the mechanistic basis of this remains undetermined. We identified altered SFPQ splicing in ALS, increasing the expression of an alternative mRNA isoform lacking a nuclear localisation sequence, which we termed ‘altSFPQ’. We find that altSFPQ mRNA contributes to SFPQ autoregulation and is highly unstable yet exhibits context-specific translation with cytoplasm-predominant localisation. Notably, reduced canonical SFPQ coincides with increased altSFPQ transcript expression in familial and sporadic ALS models, providing a mechanistic basis for SFPQ nuclear-to-cytoplasmic mislocalisation in ALS patients. Finally, we observe that altSFPQ protein has reduced phase separation potential and differential protein binding compared to its canonical counterpart, providing insight into its mechanistic relevance to ALS.
HostingRepository	PRIDE
AnnounceDate	2025-09-01
AnnouncementXML	Submission_2025-08-31_18:58:20.688.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-01 03:17:28	ID requested
⏵ 1	2025-08-31 18:58:21	announced

10.1126/sciadv.adt4814;

Neeves J, Petri, ć, Howe M, Ziff OJ, Callaghan B, Jutzi D, Pal K, Roumeliotis TI, Choudhary J, Isaacs AM, Rigo F, Bennett CF, Ruepp MD, Patani R, An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS. Sci Adv, 11(34):eadt4814(2025) [pubmed]

submitter keyword: Cytoplasmic SFPQ isoform, ALS

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
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/2025/09/PXD051918

PRIDE project URI

• PRIDE
  1. PXD051918
     1. Label: PRIDE project
     2. Name: An alternative cytoplasmic SFPQ isoform with divergent phase separation potential is upregulated in ALS