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PXD043752-1

PXD043752 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates ageing in mice
DescriptionNucleolar stress (NS) kills cells by p53-dependent and independent manners. To investigate the mechanisms of p53-indendendent toxicity, we here used (PR)n arginine-rich peptides as inducers of NS, which are found in patients of some neurodegenerative diseases. Although these peptides generate NS, how this translates to toxicity is poorly understood. We here reveal that whereas (PR)n expression leads to an overall decrease in protein abundance for the majority of the proteome, this occurs concomitant to an accumulation of free ribosomal proteins in the cytoplasm, which is a hallmark of ribosomopathies. Conversely, cells with acquired resistance to (PR)n peptides present a global downregulation of ribosomal proteins and low levels of mTOR signaling. In mice, systemic expression of (PR)97 drives widespread NS and accelerated ageing, associated to an increased expression of ribosomal proteins and mTOR hyperactivation. Furthermore, the progeroid phenotype of (PR)97-expressing mice is alleviated by rapamycin. Importantly, we show that the generalized accumulation of free ribosomal proteins is not restricted to (PR)n peptides, but is a common outcome in response to chemical or genetic perturbations that generate NS such as Actinomycin D, TIF-IA depletion or the expression or mutant HMGB1 forms recently associated to rare human diseases. Together, our study provides in vivo evidence for the role of NS as a driver of ageing in mammals, and describes a general model to understand the mechanisms behind p53-independent cell toxicity caused by NS.
HostingRepositoryPRIDE
AnnounceDate2024-03-11
AnnouncementXMLSubmission_2024-03-11_05:13:05.175.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPilar Ximenez-Embun
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF; Q Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-13 04:51:29ID requested
12024-03-11 05:13:05announced
22024-10-22 06:32:54announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Nucleolar stress, Translation, Ribosomopathy, DPRs, mTOR
Contact List
Marta Isasa
contact affiliationProteómica Centro Nacional de Investigaciones Oncológicas, CNIO Spain
contact emailmisasa@cnio.es
lab head
Pilar Ximenez-Embun
contact affiliationProteomics Group
contact emailmpximenez@cnio.es
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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