ArticleNature communications2021
Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Genetic and Phenotypic Features of the Five Known Polyaminopathies: A Critical Narrative Review.American journal of medical genetics. Part A · 2026Review
- Rapgef1 paralog-mediated regulation of Wnt/β-catenin signaling orchestrates early embryo tissue patterning and morphogenesis.Cell communication and signaling : CCS · 2026Article
- EIF5A Couples Translational Control With Transcriptional Reprogramming Through Chromocenter Reorganization During Spermiogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Crystallographic fragment screening supports tool compound discovery and reveals conformational flexibility in human deoxyhypusine synthase.Communications chemistry · 2026Article
- Case Report: A new patient expanding the clinical spectrum ofFrontiers in pediatrics · 2026Article
- Axonal Eif5a hypusination controls local translation and mitigates defects in FUS-ALS.Nature neuroscience · 2026Article
- eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy.Journal of neurodevelopmental disorders · 2025Review
- Collection, preparation, and biobanking of clinical specimens for analysis in polyaminopathies.Methods in enzymology · 2025Article
- Analysis of translational regulation using polysome profiling and puromycin incorporation.Methods in enzymology · 2025Article
- Diagnostic yield of exome sequencing-based copy number variation analysis in Mendelian disorders: a clinical application.BMC medical genomics · 2024Article
- Deoxyhypusine synthase deficiency syndrome zebrafish model: aberrant morphology, epileptiform activity, and reduced arborization of inhibitory interneurons.Molecular brain · 2024Article
- Bayesian estimation of gene constraint from an evolutionary model with gene features.Nature genetics · 2024Article
- The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.International journal of molecular sciences · 2024Review
- Structural Insights into the Mechanisms Underlying Polyaminopathies.International journal of molecular sciences · 2024Review
- Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.Nature cell biology · 2024Article
- Association between de novo variants of nuclear-encoded mitochondrial-related genes and undiagnosed developmental disorder and autism.QJM : monthly journal of the Association of Physicians · 2024Article
- Bayesian estimation of gene constraint from an evolutionary model with gene features.bioRxiv : the preprint server for biology · 2024Article
- Bachmann-Bupp syndrome and treatment.Developmental medicine and child neurology · 2024Review
- Enhancing the Spermidine Synthase-Based Polyamine Biosynthetic Pathway to Boost Rapid Growth in Marine DiatomBiomolecules · 2024Article
- Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.American journal of human genetics · 2024Article
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24 authors at 11 institutions in 4 countries.
Funding
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.
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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.