PXD046476

PXD046476 is an original dataset announced via ProteomeXchange.

Title	Unfolded Protein Response governs an Alternative Splicing program conserved from healthy to malignant cells
Description	The unfolded protein response (UPR) is a critical adaptive program triggered upon cellular stresses that profoundly reshapes the transcriptome and translatome. In the very first minutes of cellular stress, translation blockage, RNA decay and RNA granules formation prompt the synthesis of proteins essential to the stress response. Due to the dynamic nature of these processes and ribosome stalling, investigating translation upon stress has proven to be challenging; therefore, our understanding of these mechanisms and translatome rewiring upon stress remains limited. Here, we exploited O-Propargyl-puromycin (OPP) labelling of de novo peptides followed by LC-MS/MS to identify de novo proteins translated upon endoplasmic reticulum stress. Our approach combined to transcriptomic analyses revealed the synthesis of core splicing factor proteins and a profound reshaping of the splicing landscape upon ER stress. We identified a signature of 8 splicing events systematically occurring in eukaryotic cells exposed to ER stress. Using pharmacological, genetic, phosphoproteomic and sequencing approaches, we demonstrated that this specific ERsplice signature is driven by PERK activation and is dependent on splicing factors’ phosphorylation. Our study unveils a new role for ER stress and PERK in splicing regulation, and provide a molecular signature of ER stress through an ERsplice signature conserved from healthy to malignant tissues.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_17:25:26.516.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD046476
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pedro Casado-Izquierdo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-29 11:30:33	ID requested
⏵ 1	2026-09-06 17:25:27	announced

Philippe C, Burke S, Carrasco-Leon A, Martisova A, Casado P, Maniati E, Castorena J, Protopapa P, Fronk A, Chi RA, Boniface R, Rajeeve V, Dodel M, Galv, ã, o B, Aubry M, Georgieva KS, Di Bella D, Papas BN, Floyd T, Anderson K, Akerman M, Wang J, Stojic L, Mardakheh F, Morgan M, Chevet E, Touriol C, Cutillas PR, Rouault-Pierre K, PERK orchestrates an endoplasmic reticulum stress alternative splicing program via CLK1/SRSF1. Nat Commun, 17(1):(2026) [pubmed]

10.1038/s41467-026-74397-y;

10.6019/PXD046476;

submitter keyword: PERK, ER stress, alternative splicing,Unfolded protein response, translation

Pedro R. Cutillas
contact affiliation	Cell Signalling and Proteomics Group, Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, EC1M6BQ, UK
contact email	p.cutillas@qmul.ac.uk
lab head
Pedro Casado-Izquierdo
contact affiliation	Cell Signalling
contact email	p.m.casado-izquierdo@qmul.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046476
     1. Label: PRIDE project
     2. Name: Unfolded Protein Response governs an Alternative Splicing program conserved from healthy to malignant cells