PXD017253

PXD017253 is an original dataset announced via ProteomeXchange.

Title	IMPAIRED CHONDROCYTE U3 SNORNA EXPRESSION IN OSTEOARTHRITIS AND ITS IMPACT ON THE CHONDROCYTE’S PROTEIN TRANSLATION APARATUS
Description	Osteoarthritis (OA) is a chronic debilitating joint disease which is strongly associated with ageing. OA involves pathological cellular processes in all joint structures and affects articular cartilage integrity, leading to dysfunctional joint articulation. The biomolecular processes that catalyze the disturbances in the articular chondrocyte phenotype leading to OA are poorly understood, and it is expected that a comprehensive understanding of the avenues leading to catabolic changes and disruption of articular chondrocyte homeostasis will provide important cues for future treatments of the condition. Chondrocytes are specialized secretory cells with highly active protein translational machinery, enabling the synthesis and maintenance of the protein-rich cartilage extracellular matrix (ECM). Disturbances in chondrocyte protein translation in cartilage development and OA are connected to mTOR activity, ER stress, unfolded protein response (UPR)and CHOP-mediated apoptosis. These responses change the downstream translational activity of the biosynthesized ribosome. The assembled mammalian ribosome is built from ribosomal RNAs (rRNAs), together with more than 80 different protein subunits. At the heart of the ribosome, the 18S rRNA guides the decoding of the mRNA message, while an ancient ribozyme activity in the 28S rRNA forms the core of the peptidyltransferase center that polymerizes the amino acid sequence encoded by the mRNA into functional proteins. Post-transcriptional maturation of rRNAs is an integral part of the biosynthesis of ribosomes and ribonucleolytic processing of the major 47S rRNA precursor into mature 18S, 5.8S, and 28S rRNAs is rate limiting for ribosome biogenesis. The U3 small nucleolar RNA (snoRNA) is an evolutionarily highly conserved box C/D-class snoRNA which catalyzes the endoribonucleolytic processing of the 5’ external transcribed spacer (ETS) of the 47S pre-rRNA by base complementarity-guided pre-rRNA substrate recognition and plays a crucial role in the maturation of 18S rRNA. Although extensively studied in yeast, it was only recently demonstrated that U3 snoRNA is indispensable for rRNA maturation in human cells. Pathways controlling ribosome activity have previously been described in the regulation of chondrocyte homeostasis. We here now postulate that not only ribosome activity is involved in chondrocyte homeostasis, but that OA pathophysiological situations can also cause alterations in chondrocyte ribosome biogenesis with consequences for cellular protein translation. Since U3 snoRNA-driven rRNA production is rate-limiting in ribosome biogenesis, we hypothesized that the U3 snoRNA is critical for chondrocyte homeostasis. In this study we therefor aimed to determine whether OA pathophysiological conditions interact with chondrocyte U3 snoRNA levels, thereby influencing rRNA levels and chondrocyte translation capacity.
HostingRepository	PRIDE
AnnounceDate	2020-08-21
AnnouncementXML	Submission_2020-08-20_22:45:00.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD017253
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Aibek Smagul
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-22 05:15:52	ID requested
⏵ 1	2020-08-20 22:45:01	announced

Ripmeester EGJ, Caron MMJ, van den Akker GGH, Surtel DAM, Cremers A, Balaskas P, Dyer P, Housmans BAC, Chabronova A, Smagul A, Fang Y, van Rhijn LW, Peffers MJ, Welting TJM, Impaired chondrocyte U3 snoRNA expression in osteoarthritis impacts the chondrocyte protein translation apparatus. Sci Rep, 10(1):13426(2020) [pubmed]

submitter keyword: snoRNA, osteoarthritis, translation

Mandy Jayne Peffers
contact affiliation	Musculoskeletal Biology 1, Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom.
contact email	peffs@liverpool.ac.uk
lab head
Aibek Smagul
contact affiliation	University of Liverpool
contact email	aibek@liverpool.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017253
     1. Label: PRIDE project
     2. Name: IMPAIRED CHONDROCYTE U3 SNORNA EXPRESSION IN OSTEOARTHRITIS AND ITS IMPACT ON THE CHONDROCYTE’S PROTEIN TRANSLATION APARATUS