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dc.contributor.authorBaxter, Matthew
dc.contributor.authorVoronkov, Maria
dc.contributor.authorPoolman, Toryn
dc.contributor.authorGalli, Gina
dc.contributor.authorPinali, Christian
dc.contributor.authorGoosey, Laurence
dc.contributor.authorKnight, Abigail
dc.contributor.authorKrakowiak, Karolina
dc.contributor.authorMaidstone, Robert
dc.contributor.authorIqbal, Mudassar
dc.contributor.authorZi, Min
dc.contributor.authorPrehar, Sukhpal
dc.contributor.authorCartwright, Elizabeth J
dc.contributor.authorGibbs, Julie
dc.contributor.authorMatthews, Laura C
dc.contributor.authorAdamson, Antony D
dc.contributor.authorHumphreys, Neil E
dc.contributor.authorRebelo-Guiomar, Pedro
dc.contributor.authorMinczuk, Michal
dc.contributor.authorBechtold, David A
dc.contributor.authorLoudon, Andrew
dc.contributor.authorRay, David
dc.date.accessioned2020-02-06T05:13:29Z
dc.date.available2020-02-06T05:13:29Z
dc.date.issued2020-01-15
dc.date.submitted2019-07-30
dc.identifier.other50705
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301773
dc.description.abstractEfficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5’UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5’UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectCell Biology
dc.subjectmitochondria
dc.subjectprotein translation
dc.subjectcardiac
dc.subjectribosome
dc.subjectHuman
dc.subjectMouse
dc.titleCardiac mitochondrial function depends on BUD23 mediated ribosome programming
dc.typeArticle
dc.date.updated2020-02-06T05:13:28Z
prism.publicationNameeLife, volume 9
dc.identifier.doi10.17863/CAM.48847
dcterms.dateAccepted2019-12-24
rioxxterms.versionofrecord10.7554/elife.50705
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Topf, Ulrike
datacite.contributor.supervisorsenior_editor: Stainier, Didier YR
dc.contributor.orcidBaxter, Matthew [0000-0002-3612-2574]
dc.contributor.orcidVoronkov, Maria [0000-0001-5636-9892]
dc.contributor.orcidMinczuk, Michal [0000-0001-8242-1420]
dc.identifier.eissn2050-084X
pubs.funder-project-idMedical Research Council (MR/L010240/1)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)