Evidence map›Paper›PMID 40128524›Full record

ArticleNature communications2025

Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis.

Alexandra E Preston, Joe N Frost, Megan R Teh, Mohsin Badat, Andrew E Armitage, Ruggiero Norfo, Sarah K Wideman, Muhammad Hanifi, Natasha White, Noémi Ba Roy and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Alexandra E PrestonMRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. alexandra.preston@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0003-0008-5916
Joe N FrostMRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-5946-6062
Megan R TehMRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8095-9961
Mohsin BadatMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-0744-5427
Andrew E ArmitageMRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5977-6602
Ruggiero NorfoMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Sarah K WidemanMRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-7803-9894
Muhammad HanifiMRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Natasha WhiteMRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5793-892X
Noémi Ba RoyMRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Christian BabbsMRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1898-5878
Bart GhesquiereMetabolomics Expertise Center, VIB Center for Cancer Biology, Katholieke Universiteit Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-1547-1705
James DaviesMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-4108-4357
Andrew Jm HowdenDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
Linda V SinclairDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.ORCID http://orcid.org/0000-0003-1248-7189
Jim R HughesMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8955-7256
Mira KassoufMRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9781-921X
Rob BeagrieWellcome Centre for Human Genetics, University of Oxford, Oxford, UK. robert.beagrie@well.ox.ac.uk.ORCID http://orcid.org/0000-0003-1076-5595
Douglas R HiggsMRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-3579-8705
Hal DrakesmithMRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. alexander.drakesmith@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0002-8503-6103

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
VISION: ValIdated Systematic IntegratiON of epigenomic dataR24DK106766 · NIDDK · PENNSYLVANIA STATE UNIVERSITY, THE · PI BLOBEL, GERD A, BODINE, DAVID M. · 2016 to 2020
$6.2M
NCI NIH HHS P30 CA008748NIDDK NIH HHS R24 DK106766Wellcome Trust 225220
6 · The paper itself

Abstract

Red blood cell development from erythroid progenitors requires profound reshaping of metabolism and gene expression. How these transcriptional and metabolic alterations are coupled is unclear. Nprl3 (an inhibitor of mTORC1) has remained in synteny with the α-globin genes for >500 million years, and harbours most of the a-globin enhancers. However, whether Nprl3 serves an erythroid role is unknown. We found that while haematopoietic progenitors require basal Nprl3 expression, erythroid Nprl3 expression is further boosted by the α-globin enhancers. This lineage-specific upregulation is required for sufficient erythropoiesis. Loss of Nprl3 affects erythroblast metabolism via elevating mTORC1 signalling, suppressing autophagy and disrupting glycolysis. Broadly consistent with these murine findings, human NPRL3-knockout erythroid progenitors produce fewer enucleated cells and demonstrate dysregulated mTORC1 signalling in response to nutrient availability and erythropoietin. Therefore, we propose that the anciently conserved linkage of NprI3, α-globin and their associated enhancers has coupled metabolic and developmental control of erythropoiesis.

Indexed as

alpha-GlobinsErythropoiesisTumor Suppressor ProteinsAnimalsAutophagyEnhancer Elements, GeneticErythroblastsErythroid Precursor CellsErythropoietinGlycolysisHumansMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, KnockoutSignal Transductionalpha-GlobinsErythropoietinMechanistic Target of Rapamycin Complex 1Tumor Suppressor Proteins

Identifiers

PMID40128524
PMCPMC11933693

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.