ArticleNature communications2020
DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.Nature genetics · 2025Pooled it
- Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications.Nature genetics · 2023Pooled it
- Advancements in the Understanding of the Genetics of Obsessive-Compulsive Disorder (OCD).Current psychiatry reports · 2026Review
- Untargeted Metabolomic Profiling Identifies Breed-Specific Metabolomic Signatures in the Longissimus Dorsi Meat of Beichuan White Goats and Tianfu Goats.Metabolites · 2026Article
- tRNA methylation: functional insights and epitranscriptomic regulation.Cell communication and signaling : CCS · 2026Review
- RNA methylation in autoimmune rheumatic diseases: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Reconnaissance of the Good, the Bad, and the Ugly Role of tRNAs in Carcinogenesis and Metastasis.Experientia supplementum (2012) · 2026Review
- The methyltransferase-like proteins as core regulators of nucleic acid modifications and post-translation modification of proteins in disease pathogenesis and therapeutic implications.Biomarker research · 2025Review
- Nanopore direct RNA sequencing reveals METTL2A-mediated mGenome research · 2025Article
- RNA methylation in hepatocellular carcinoma: from metabolic reprogramming and immune escape mechanisms to small molecule inhibitor development.Journal of translational medicine · 2025Review
- ADAT3 variants disrupt the activity of the ADAT tRNA deaminase complex and impair neuronal migration.Brain : a journal of neurology · 2025Article
- Targeting tRNA methyltransferases: from molecular mechanisms to drug discovery.Science China. Life sciences · 2025Review
- Structural Impact of 3-methylcytosine Modification on the Anticodon Stem-loop of a Neuronally-enriched Arginine tRNA.Journal of molecular biology · 2025Article
- Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation.Stem cell research & therapy · 2025Article
- Bi-allelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a neurodevelopmental disorder.American journal of human genetics · 2025Article
- Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.medRxiv : the preprint server for health sciences · 2025Article
- Human TRMT1 and TRMT1L paralogs ensure the proper modification state, stability, and function of tRNAs.Cell reports · 2025Article
- tRNA and tsRNA: From Heterogeneity to Multifaceted Regulators.Biomolecules · 2024Review
- Analyses of GWAS signal using GRIN identify additional genes contributing to suicidal behavior.Communications biology · 2024Article
- tRNA modifications and tRNA-derived small RNAs: new insights of tRNA in human disease.Cell biology and toxicology · 2024Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
In mammals, a subset of arginine tRNA isoacceptors are methylated in the anticodon loop by the METTL2 methyltransferase to form the 3-methylcytosine (m3C) modification. However, the mechanism by which METTL2 identifies specific tRNA arginine species for m3C formation as well as the biological role of m3C in mammals is unknown. Here, we show that human METTL2 forms a complex with DALR anticodon binding domain containing 3 (DALRD3) protein to recognize particular arginine tRNAs destined for m3C modification. DALRD3-deficient human cells exhibit nearly complete loss of the m3C modification in tRNA-Arg species. Notably, we identify a homozygous nonsense mutation in the DALRD3 gene that impairs m3C formation in human patients exhibiting developmental delay and early-onset epileptic encephalopathy. These findings uncover an unexpected function for the DALRD3 protein in the targeting of distinct arginine tRNAs for m3C modification and suggest a crucial biological role for DALRD3-dependent tRNA modification in proper neurological development.
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Registered trials
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.