Skip to content

Opening book details…

Can I read Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine on EtoBox?

Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine by Faundes, Víctor (author);Jennings, Martin D. (author);Crilly, Siobhan (author);Legraie, Sarah (author);Withers, Sarah E. (author);Cuvertino, Sara (author);Davies, Sally J. (author);Douglas, Andrew G. L. (author);Fry, Andrew E. (author);Harrison, Victoria (author);Amiel, Jeanne (author);Lehalle, Daphné (author);Newman, William G. (author);Newkirk, Patricia (author);Ranells, Judith (author);Splitt, Miranda (author);Cross, Laura A. (author);Saunders, Carol J. (author);Sullivan, Bonnie R. (author);Granadillo, Jorge L. (author);Gordon, Christopher T. (author);Kasher, Paul R. (author);Pavitt, Graham D. (author);Banka, Siddharth (author) is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine about?

## Abstract The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles and restores expression of PPT reporters. In zebrafish, knockdown eif5a partly recapitulates the human phenotype that can be rescued with 1 μM spermidine supplementation. In summary, we uncover the role of eIF5A in human development and disease, demonstrate the mechanistic complexity of EIF5A-related disorder and raise possibilities for its treatment.

Who reads Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine?

It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.

Author
Faundes, Víctor (author);Jennings, Martin D. (author);Crilly, Siobhan (author);Legraie, Sarah (author);Withers, Sarah E. (author);Cuvertino, Sara (author);Davies, Sally J. (author);Douglas, Andrew G. L. (author);Fry, Andrew E. (author);Harrison, Victoria (author);Amiel, Jeanne (author);Lehalle, Daphné (author);Newman, William G. (author);Newkirk, Patricia (author);Ranells, Judith (author);Splitt, Miranda (author);Cross, Laura A. (author);Saunders, Carol J. (author);Sullivan, Bonnie R. (author);Granadillo, Jorge L. (author);Gordon, Christopher T. (author);Kasher, Paul R. (author);Pavitt, Graham D. (author);Banka, Siddharth (author)
Publisher
Springer Science and Business Media LLC
Published
2021
Language
EN
Field
Biochemistry, Genetics and Molecular Biology (Life Sciences)

More by Faundes, Víctor (author);Jennings, Martin D. (author);Crilly, Siobhan (author);Legraie, Sarah (author);Withers, Sarah E. (author);Cuvertino, Sara (author);Davies, Sally J. (author);Douglas, Andrew G. L. (author);Fry, Andrew E. (author);Harrison, Victoria (author);Amiel, Jeanne (author);Lehalle, Daphné (author);Newman, William G. (author);Newkirk, Patricia (author);Ranells, Judith (author);Splitt, Miranda (author);Cross, Laura A. (author);Saunders, Carol J. (author);Sullivan, Bonnie R. (author);Granadillo, Jorge L. (author);Gordon, Christopher T. (author);Kasher, Paul R. (author);Pavitt, Graham D. (author);Banka, Siddharth (author)

Browse all works by Faundes, Víctor (author);Jennings, Martin D. (author);Crilly, Siobhan (author);Legraie, Sarah (author);Withers, Sarah E. (author);Cuvertino, Sara (author);Davies, Sally J. (author);Douglas, Andrew G. L. (author);Fry, Andrew E. (author);Harrison, Victoria (author);Amiel, Jeanne (author);Lehalle, Daphné (author);Newman, William G. (author);Newkirk, Patricia (author);Ranells, Judith (author);Splitt, Miranda (author);Cross, Laura A. (author);Saunders, Carol J. (author);Sullivan, Bonnie R. (author);Granadillo, Jorge L. (author);Gordon, Christopher T. (author);Kasher, Paul R. (author);Pavitt, Graham D. (author);Banka, Siddharth (author)