PXD065723

PXD065723 is an original dataset announced via ProteomeXchange.

Title	Deciphering nuclear polyp function during human cell proliferation
Description	Nuclear speckles (NS) are membrane-less nuclear organelles that act as critical hubs for pre-mRNA splicing. Defects in splicing are linked to several human diseases, including cancer, Alzheimer's disease, and dystrophies. While CLK kinases regulate the mobilization of splicing factors from NS, the molecular mechanisms underlying NS assembly and dissolution remain unclear. Using an adaptation of the Biotinylation by Antibody Recognition (BAR) technique, we identify polyphosphate (polyP) as a novel and essential regulator of NS dynamics. Polyphosphate, a highly conserved polyanion composed of a chain of phosphate molecules, is involved in several functions in mammalian cells. Here, we show that polyP interacts with the NS core component SRRM2, and polyP depletion disrupts NS organization releasing splicing factors into the nucleoplasm. RNA-seq analysis reveals that polyP depletion increases exon inclusion, particularly in long genes with multiple exons, highlighting its role in splicing regulation. Mechanistically, we demonstrate that polyP acts as a physiological inhibitor of CLK3 kinase, preventing the phosphorylation of SR proteins and thereby maintaining NS stability. Our findings not only expand our understanding of NS biology but also provide new insights into the polyP involvement in splicing-related diseases.
HostingRepository	PRIDE
AnnounceDate	2026-03-13
AnnouncementXML	Submission_2026-03-13_07:41:31.699.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD065723
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Concha Gil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-03 03:07:32	ID requested
⏵ 1	2026-03-13 07:41:32	announced

10.6019/PXD065723;

submitter keyword: Polyphosphate, PPBD, nuclear speckle, SRRM2, proximity labelling

Josep Clotet
contact affiliation	Universitat Internacional de Catalunya, Barcelona, Spain.
contact email	jclotet@uic.es
lab head
Concha Gil
contact affiliation	UCM
contact email	cai.proteomica@pas.ucm.es
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/2026/03/PXD065723

PRIDE project URI

• PRIDE
  1. PXD065723
     1. Label: PRIDE project
     2. Name: Deciphering nuclear polyp function during human cell proliferation