ArticleNucleic acids research2025
Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Isoleucine absence from adult human hemoglobin is mirrored in mosquito proteomes and limits malaria parasite growth.bioRxiv : the preprint server for biology · 2026Article
- Review
- Aminoacyl-tRNA Synthetases: Variant Classification, Functional Assays, and Emerging Therapeutic Strategies.Journal of inherited metabolic disease · 2026Review
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- Codon-specific ribosome stalling reshapes translational dynamics during branched-chain amino acid starvation.Genome biology · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
Aminoacyl-tRNA synthetases (ARSs) couple tRNAs with their corresponding amino acids. While ARSs can bind structurally similar amino acids, extreme specificity is ensured by subsequent editing activity. Yet, we found that upon isoleucine (I) restriction, healthy fibroblasts consistently incorporated valine (V) into proteins at isoleucine codons, resulting from misacylation of tRNAIle with valine by wildtype IARS1. Using a dual-fluorescent reporter of translation, we found that valine supplementation could fully compensate for isoleucine depletion and restore translation to normal levels in healthy, but not IARS1 deficient cells. Similarly, the antiproliferative effects of isoleucine deprivation could be fully restored by valine supplementation in healthy, but not IARS1 deficient cells. This indicates I > V substitutions help prevent translational termination and maintain cellular function in human primary cells during isoleucine deprivation. We suggest that this is an example of a more general mechanism in mammalian cells to preserve translational speed at the cost of translational fidelity in response to (local) amino acid deficiencies.
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Registered trials
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