PXD015218

PXD015218 is an original dataset announced via ProteomeXchange.

Title	Identification of RPL9 variants incorporated in mature ribosomes from patient's Lymphoblastoid cell line
Description	Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5’UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80 monosome reductions, the downstream effects are remarkably different. Cells carrying the 5’UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, cells carrying the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5’UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts.
HostingRepository	PRIDE
AnnounceDate	2019-12-10
AnnouncementXML	Submission_2019-12-10_00:55:47.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD015218
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Hesse Anne-Marie
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-29 05:38:45	ID requested
⏵ 1	2019-12-10 00:55:49	announced

Lezzerini M, Penzo M, O'Donohue MF, Marques Dos Santos Vieira C, Saby M, Elfrink HL, Diets IJ, Hesse AM, Cout, é Y, Gastou M, Nin-Velez A, Nikkels PGJ, Olson AN, Zonneveld-Huijssoon E, Jongmans MCJ, Zhang G, van Weeghel M, Houtkooper RH, Wlodarski MW, Kuiper RP, Bierings MB, van der Werff Ten Bosch J, Leblanc T, Montanaro L, Dinman JD, Da Costa L, Gleizes PE, MacInnes AW, Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism. Nucleic Acids Res, 48(2):770-787(2020) [pubmed]

submitter keyword: ribosomes, RPL9 variants, nanoLC-MS/MS, label-free quantification

Virginie Brun
contact affiliation	Univ. Grenoble Alpes, CEA, INSERM, IRIG, BGE, F-38000 Grenoble, France
contact email	virginie.brun@cea.fr
lab head
Hesse Anne-Marie
contact affiliation	Laboratoire d'Etude de la Dynamique des Protéomes
contact email	anne-marie.hesse@cea.fr
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/2019/12/PXD015218

PRIDE project URI

• PRIDE
  1. PXD015218
     1. Label: PRIDE project
     2. Name: Identification of RPL9 variants incorporated in mature ribosomes from patient's Lymphoblastoid cell line