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Cardiac mitochondrial function depends on BUD23 mediated ribosome programming

Baxter, M; Voronkov, M; Poolman, T; Galli, G; Pinali, C; Goosey, L; Knight, A; ... Ray, D; + view all (2020) Cardiac mitochondrial function depends on BUD23 mediated ribosome programming. eLife , 9 , Article e50705. 10.7554/eLife.50705. Green open access

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Abstract

Efficient 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.

Type: Article
Title: Cardiac mitochondrial function depends on BUD23 mediated ribosome programming
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.50705
Publisher version: https://doi.org/10.7554/eLife.50705
Language: English
Additional information: Copyright © Baxter et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10103182
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