Nature Communications (Feb 2021)
Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine
- Víctor Faundes,
- Martin D. Jennings,
- Siobhan Crilly,
- Sarah Legraie,
- Sarah E. Withers,
- Sara Cuvertino,
- Sally J. Davies,
- Andrew G. L. Douglas,
- Andrew E. Fry,
- Victoria Harrison,
- Jeanne Amiel,
- Daphné Lehalle,
- William G. Newman,
- Patricia Newkirk,
- Judith Ranells,
- Miranda Splitt,
- Laura A. Cross,
- Carol J. Saunders,
- Bonnie R. Sullivan,
- Jorge L. Granadillo,
- Christopher T. Gordon,
- Paul R. Kasher,
- Graham D. Pavitt,
- Siddharth Banka
Affiliations
- Víctor Faundes
- Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Martin D. Jennings
- Division of Molecular and Cellular Function, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Siobhan Crilly
- Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Sarah Legraie
- Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Sarah E. Withers
- Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Sara Cuvertino
- Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Sally J. Davies
- Institute of Medical Genetics, University Hospital of Wales
- Andrew G. L. Douglas
- Wessex Clinical Genetics Service, Princess Anne Hospital
- Andrew E. Fry
- Institute of Medical Genetics, University Hospital of Wales
- Victoria Harrison
- Wessex Clinical Genetics Service, Princess Anne Hospital
- Jeanne Amiel
- Department of Genetics, AP-HP, Hôpital Necker Enfants Malades
- Daphné Lehalle
- Department of Genetics, AP-HP, Hôpital Necker Enfants Malades
- William G. Newman
- Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Patricia Newkirk
- Division of Genetics and Metabolism, Department of Pediatrics, University of South Florida
- Judith Ranells
- Division of Genetics and Metabolism, Department of Pediatrics, University of South Florida
- Miranda Splitt
- Northern Genetics Service, Institute of Genetic Medicine
- Laura A. Cross
- Division of Clinical Genetics, Children’s Mercy
- Carol J. Saunders
- Center for Pediatric Genomic Medicine Children’s Mercy
- Bonnie R. Sullivan
- Division of Clinical Genetics, Children’s Mercy
- Jorge L. Granadillo
- Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine
- Christopher T. Gordon
- 1Laboratory of Embryology and Genetics of Human Malformations, INSERM UMR 1163, Institut Imagine
- Paul R. Kasher
- Manchester Academic Health Science Centre, University of Manchester
- Graham D. Pavitt
- Division of Molecular and Cellular Function, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- Siddharth Banka
- Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
- DOI
- https://doi.org/10.1038/s41467-021-21053-2
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 13
Abstract
eIF5A is critical for protein synthesis but has not yet been associated with congenital human disease. Here, the authors show that EIF5A variants cause a Mendelian disorder via reduced eIF5A-ribosome interactions and this phenotype is partially corrected by spermidine supplementation in yeast and zebrafish.
