PXD060557

PXD060557 is an original dataset announced via ProteomeXchange.

Title	Ancient genomic linkage of alpha-globin and Nprl3 couples metabolism with erythropoiesis
Description	Development of red blood cells from progenitors requires profound reshaping of both gene expression and metabolism. How these processes are coupled is unclear. Nprl3, an inhibitor of mTORC1, has remained in synteny with the -globin genes for >500 million years, and harbours most of the -globin enhancers. However, whether Nprl3 itself serves an erythroid role is unknown. While hematopoietic progenitors rely on tonic expression of baseline Nprl3, erythroblasts experience ‘boosted’ Nprl3 expression. Using Nprl3-deficient fetal liver and adult competitive bone marrow - fetal liver chimaeras, we show that NprI3 is required for sufficient erythropoiesis. Loss of Nprl3 elevates mTORC1 signalling, suppresses autophagy and disrupts erythroblast glycolysis. Human NPRL3-knockout erythroid progenitors produce fewer enucleated cells and demonstrate dysregulated mTORC1 signalling in response to nutrient availability and erythropoietin. Thus, Nprl3 is a key regulator of erythroid metabolism. Finally, we show that the alpha-globin enhancers upregulate erythoid NprI3 expression, and that this activity supports optimal erythropoiesis.
HostingRepository	PRIDE
AnnounceDate	2025-02-12
AnnouncementXML	Submission_2025-02-12_05:29:46.231.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Howden
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-06 13:36:06	ID requested
⏵ 1	2025-02-12 05:29:46	announced

Dataset with its publication pending

submitter keyword: red blood cells, Nprl3, erythropoiesis

Professor Hal Drakesmith
contact affiliation	MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK
contact email	alexander.drakesmith@ndm.ox.ac.uk
lab head
Andrew Howden
contact affiliation	University of Dundee
contact email	a.howden@dundee.ac.uk
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/2025/02/PXD060557

PRIDE project URI

• PRIDE
  1. PXD060557
     1. Label: PRIDE project
     2. Name: Ancient genomic linkage of alpha-globin and Nprl3 couples metabolism with erythropoiesis