ArticlePLoS genetics2014
Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications.Frontiers in endocrinology · 2022Pooled it
- Review
- MiaA-mediated tRNA modifications couple tryptophan attenuation and changes in tRNA abundance to complex phenotypes in Pseudomonas aeruginosa.Nucleic acids research · 2026Article
- Defective queuosine and i6A/ms2i6A modification of tRNATyr cause frameshifting and protein aggregation.Nucleic acids research · 2026Article
- Article
- From chromatin to proteostasis: multilevel gene regulation in Mendelian diseases.Frontiers in epigenetics and epigenomics · 2026Review
- Cytokinins Are Age- and Injury-Responsive Molecules That Regulate Skeletal Myogenesis.International journal of molecular sciences · 2025Article
- Transcription, Maturation and Degradation of Mitochondrial RNA: Implications for Innate Immune Response.Biomolecules · 2025Review
- Selenium and selenoproteins: key regulators of ferroptosis and therapeutic targets in cancer.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Mitochondrial tRNA modifications: functions, diseases caused by their loss, and treatment strategies.RNA (New York, N.Y.) · 2025Review
- Article
- Article
- Bioorthogonal labeling and profiling of N6-isopentenyladenosine (i6A) modified RNA.Nucleic acids research · 2024Article
- Deficient tRNA posttranscription modification dysregulated the mitochondrial quality controls and apoptosis.iScience · 2024Article
- Genetic etiology of progressive pediatric neurological disorders.Pediatric research · 2024Article
- Arginine to glutamine mutation in the substrate binding region impaired the isopentenyl activity ofMolecular biology research communications · 2024Article
- Coordination of RNA modifications in the brain and beyond.Molecular psychiatry · 2023Review
- The life and times of a tRNA.RNA (New York, N.Y.) · 2023Review
- Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models.International journal of molecular sciences · 2023Review
- TRIT1 defect leads to a recognizable phenotype of myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and normal lactate levels.Journal of inherited metabolic disease · 2022Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 4 countries.
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Abstract
Identifying the genetic basis for mitochondrial diseases is technically challenging given the size of the mitochondrial proteome and the heterogeneity of disease presentations. Using next-generation exome sequencing, we identified in a patient with severe combined mitochondrial respiratory chain defects and corresponding perturbation in mitochondrial protein synthesis, a homozygous p.Arg323Gln mutation in TRIT1. This gene encodes human tRNA isopentenyltransferase, which is responsible for i6A37 modification of the anticodon loops of a small subset of cytosolic and mitochondrial tRNAs. Deficiency of i6A37 was previously shown in yeast to decrease translational efficiency and fidelity in a codon-specific manner. Modelling of the p.Arg323Gln mutation on the co-crystal structure of the homologous yeast isopentenyltransferase bound to a substrate tRNA, indicates that it is one of a series of adjacent basic side chains that interact with the tRNA backbone of the anticodon stem, somewhat removed from the catalytic center. We show that patient cells bearing the p.Arg323Gln TRIT1 mutation are severely deficient in i6A37 in both cytosolic and mitochondrial tRNAs. Complete complementation of the i6A37 deficiency of both cytosolic and mitochondrial tRNAs was achieved by transduction of patient fibroblasts with wild-type TRIT1. Moreover, we show that a previously-reported pathogenic m.7480A>G mt-tRNASer(UCN) mutation in the anticodon loop sequence A36A37A38 recognised by TRIT1 causes a loss of i6A37 modification. These data demonstrate that deficiencies of i6A37 tRNA modification should be considered a potential mechanism of human disease caused by both nuclear gene and mitochondrial DNA mutations while providing insight into the structure and function of TRIT1 in the modification of cytosolic and mitochondrial tRNAs.
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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 OpenQuestion graph.