PXD046699

PXD046699 is an original dataset announced via ProteomeXchange.

Title	The RNA Binding Protein HNRNPK induces p53-dependent nucleolar stress driving ribosompathy
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2025-06-04
AnnouncementXML	Submission_2025-06-04_08:59:11.336.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pilar Ximenez-Embun
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-06 04:49:38	ID requested
⏵ 1	2025-06-04 08:59:11	announced

10.1172/JCI183697;

submitter keyword: ribosomepathy, MEFs, TMT,Hnrnpk

Marta Isasa
contact affiliation	Head of the Proteomics Unit Spanish National Cancer Research Center, CNIO Melchor Fernández Almagro, 3 28029 Madrid, Spain
contact email	misasa@cnio.es
lab head
Pilar Ximenez-Embun
contact affiliation	Proteomics Group
contact email	mpximenez@cnio.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/2025/06/PXD046699

PRIDE project URI

• PRIDE
  1. PXD046699
     1. Label: PRIDE project
     2. Name: The RNA Binding Protein HNRNPK induces p53-dependent nucleolar stress driving ribosompathy