PXD051195

PXD051195 is an original dataset announced via ProteomeXchange.

Title	LINE-1 RNA triggers matrix formation in bone cells via a PKR-mediated inflammatory response
Description	Transposable elements (TEs) are mobile genetic modules of viral derivation that have been co-opted to become modulators of mammalian gene expression. TEs are a major source of endogenous dsRNAs, signaling molecules able to coordinate inflammatory responses in various physiological processes. Here, we provide evidence for a positive involvement of TEs in inflammation-driven bone repair and mineralization. In newly fractured mice bone, we observed an early transient upregulation of repeats occurring concurrently with the initiation of the inflammatory stage. In humans, bone biopsies analysis revealed a significant correlation between repeats expression, mechanical stress and bone mineral density. We investigated a potential link between LINE-1 (L1) expression and bone mineralization by delivering a synthetic L1 RNA to osteoporotic patient-derived mesenchymal stem cells and observed a dsRNA-triggered protein kinase (PKR)-mediated stress response, leading to dramatically increased mineralization. This response was associated with a strong, transient, inflammatory induction, accompanied by a global translation attenuation induced by eif2a phosphorylation. We demonstrated that L1 transfection reshaped the secretory profile of osteoblasts, triggering a paracrine activity that stimulated the mineralization of recipient cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_08:43:44.045.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dalila Bensaddek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-04 08:46:48	ID requested
⏵ 1	2024-10-17 08:43:45	announced

Mangiavacchi A, Morelli G, Reppe S, Saera-Vila A, Liu P, Eggerschwiler B, Zhang H, Bensaddek D, Casanova EA, Medina Gomez C, Prijatelj V, Della Valle F, Atinbayeva N, Izpisua Belmonte JC, Rivadeneira F, Cinelli P, Gautvik KM, Orlando V, LINE-1 RNA triggers matrix formation in bone cells via a PKR-mediated inflammatory response. EMBO J, 43(17):3587-3603(2024) [pubmed]

10.1038/s44318-024-00143-z;

submitter keyword: exosomes, PKR,transposable elements

Valerio Orlando
contact affiliation	Biological and Environmental Sciences and Engineering Division,King Abdullah University of Science and Technology
contact email	valerio.orlando@kaust.edu.sa
lab head
Dalila Bensaddek
contact affiliation	KAUST
contact email	dalila.bensaddek@kaust.edu.sa
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/2024/10/PXD051195

PRIDE project URI

• PRIDE
  1. PXD051195
     1. Label: PRIDE project
     2. Name: LINE-1 RNA triggers matrix formation in bone cells via a PKR-mediated inflammatory response