ArticleNucleic acids research2024
TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Genotype-phenotype variability in TRMT10A deficiency: divergent developmental outcomes associated with biallelic loss-of-function variants.Journal of human genetics · 2026Article
- TRMT10A maintains lipid homeostasis independently of its tRNA mScience China. Life sciences · 2026Article
- CDKAL1 dysfunction impairs lysine codon translation in podocytes and accelerates chronic kidney disease.The EMBO journal · 2026Article
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- Article
- Targeting tRNA methyltransferases: from molecular mechanisms to drug discovery.Science China. Life sciences · 2025Review
- Emerging roles of transfer RNA fragments in the CNS.Brain : a journal of neurology · 2025Review
- RNA Polymerase III-Transcribed RNAs in Health and Disease: Mechanisms, Dysfunction, and Future Directions.International journal of molecular sciences · 2025Review
- The functions and modifications of tRNA-derived small RNAs in cancer biology.Cancer metastasis reviews · 2025Review
- Curcumin reverses cognitive deficits through promoting neurogenesis and synapse plasticity via the upregulation of PSD95 and BDNF in mice.Scientific reports · 2025Article
- Decoding tRNA dynamics in neuroimmune disorders: mechanistic insights, diagnostic innovations, and therapeutic opportunities.Frontiers in immunology · 2025Review
- Human DUS1L catalyzes dihydrouridine modification at tRNA positions 16/17, and DUS1L overexpression perturbs translation.Communications biology · 2024Article
- Metabolism Meets Translation: Dietary and Metabolic Influences on tRNA Modifications and Codon Biased Translation.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
19 authors.
Funding
Abstract
In higher eukaryotes, tRNA methyltransferase 10A (TRMT10A) is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs. Pathogenic mutations in TRMT10A cause intellectual disability, microcephaly, diabetes, and short stature in humans, and generate cytotoxic tRNA fragments in cultured cells; however, it is not clear how TRMT10A supports codon translation or brain functions. Here, we generated Trmt10a null mice and showed that tRNAGln(CUG) and initiator methionine tRNA levels were universally decreased in various tissues; the same was true in a human cell line lacking TRMT10A. Ribosome profiling of mouse brain revealed that dysfunction of TRMT10A causes ribosome slowdown at the Gln(CAG) codon and increases translation of Atf4 due to higher frequency of leaky scanning of its upstream open reading frames. Broadly speaking, translation of a subset of mRNAs, especially those for neuronal structures, is perturbed in the mutant brain. Despite not showing discernable defects in the pancreas, liver, or kidney, Trmt10a null mice showed lower body weight and smaller hippocampal postsynaptic densities, which is associated with defective synaptic plasticity and memory. Taken together, our study provides mechanistic insight into the roles of TRMT10A in the brain, and exemplifies the importance of universal tRNA modification during translation of specific codons.
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