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PXD046699

PXD046699 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe RNA Binding Protein HNRNPK induces p53-dependent nucleolar stress driving ribosompathy
DescriptionThe nucleolus is the membraneless organelle in the nucleus mainly responsible for ribosome biogenesis. It is also an excellent stress sensor and any changes on its architecture or composition leads to nucleolar stress deriving in cell cycle arrest and interruption of ribosomal activity. However, nucleolar stress sustained is also a contributing factor to pathologies like aging and cancer, highlighting the importance of its homeostasis in the cells. In this study, we identified and described the pivotal role of the RNA-binding protein Hnrnpk in the ribosome biogenesis and nucleolar dynamics. We developed an in vitro model of Hnrnpk overexpression with CRISPR-Cas9/SAM and an in vivo mouse model of Hnrnpk ubiquitous overexpression. We found that this overexpression disrupted translation and caused alterations in the nucleolar structure, resulting in nucleolar stress with alterations in the levels and localization of the nucleolar components fibrillarin and nucleolin, as well as impaired ribosome biogenesis. These aberrations trigger cell cycle arrest and cell senescence, and the phenotype could be rescued with haploinsufficiency of p53, suggesting that it is a consequence of a p53-dependant nucleolar stress mechanism. Finally, in our mouse model, Hnrnpk overexpression led to an aging phenotype with bone marrow failure and reduced lifespan, similar to a ribosomopathy-like phenotype. Together, our findings identify Hnrnpk as a novel master regulator of ribosome biogenesis and nucleolar homeostasis through p53, providing a new view of the orchestration of nucleolar integrity, ribosome function and cellular senescence.
HostingRepositoryPRIDE
AnnounceDate2025-06-04
AnnouncementXMLSubmission_2025-06-04_08:59:11.336.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPilar Ximenez-Embun
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-06 04:49:38ID requested
12025-06-04 08:59:11announced
Publication List
10.1172/JCI183697;
Keyword List
submitter keyword: ribosomepathy, MEFs, TMT,Hnrnpk
Contact List
Marta Isasa
contact affiliationHead of the Proteomics Unit Spanish National Cancer Research Center, CNIO Melchor Fernández Almagro, 3 28029 Madrid, Spain
contact emailmisasa@cnio.es
lab head
Pilar Ximenez-Embun
contact affiliationProteomics Group
contact emailmpximenez@cnio.es
dataset submitter
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Dataset FTP location
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