ArticleNucleic acids research2021
THUMPD3-TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 60 citations in OpenAlex.
- Guanosine 10 methylation by TRMT11-TRMT112 optimizes human mitochondrial tRNAs for efficient translation.Nucleic acids research · 2026Article
- TRMT10A maintains lipid homeostasis independently of its tRNA mScience China. Life sciences · 2026Article
- Integrative Analysis UncoversCurrent issues in molecular biology · 2026Article
- tRNA methylation: functional insights and epitranscriptomic regulation.Cell communication and signaling : CCS · 2026Review
- Structure of the NAT10 acetyltransferase and mechanism of tRNA acetylation.Nature communications · 2026Article
- TRMT112 drives a tumor growth and metastasis-promoting program in triple-negative breast cancer.Cell death and differentiation · 2026Article
- EnterohemorrhagicmSystems · 2026Article
- Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5.Nature chemical biology · 2026Article
- 2'-O-methylation-dependent installation of NNature communications · 2026Article
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Seven wonders of RNA modification biology.RNA (New York, N.Y.) · 2026Review
- tRNA mMolecular cancer · 2026Article
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- The Rare RNA Methylations m²G, Cm, m⁵U and ms²i⁶A: Roles in Disease Pathogenesis and Emerging Therapeutic Implications.International journal of medical sciences · 2026Review
- tRNA modifications: greasing the wheels of translation and beyond.RNA biology · 2025Review
- Disrupting tRNA modifications to target mitochondrial vulnerabilities in drug-resistant leukemia cells.Blood · 2025Article
- Targeting tRNA methyltransferases: from molecular mechanisms to drug discovery.Science China. Life sciences · 2025Review
- A transfer RNA methyltransferase with an unusual domain composition catalyzes 2'-O-methylation at position 6 in tRNA.Nucleic acids research · 2025Article
- Mammalian tRNA acetylation determines translation efficiency and tRNA quality control.Nature communications · 2025Article
- MapID-based quantitative mapping of chemical modifications and expression of human transfer RNA.Cell chemical biology · 2025Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-transcriptional modifications affect tRNA biology and are closely associated with human diseases. However, progress on the functional analysis of tRNA modifications in metazoans has been slow because of the difficulty in identifying modifying enzymes. For example, the biogenesis and function of the prevalent N2-methylguanosine (m2G) at the sixth position of tRNAs in eukaryotes has long remained enigmatic. Herein, using a reverse genetics approach coupled with RNA-mass spectrometry, we identified that THUMP domain-containing protein 3 (THUMPD3) is responsible for tRNA: m2G6 formation in human cells. However, THUMPD3 alone could not modify tRNAs. Instead, multifunctional methyltransferase subunit TRM112-like protein (TRMT112) interacts with THUMPD3 to activate its methyltransferase activity. In the in vitro enzymatic assay system, THUMPD3-TRMT112 could methylate all the 26 tested G6-containing human cytoplasmic tRNAs by recognizing the characteristic 3'-CCA of mature tRNAs. We also showed that m2G7 of tRNATrp was introduced by THUMPD3-TRMT112. Furthermore, THUMPD3 is widely expressed in mouse tissues, with an extremely high level in the testis. THUMPD3-knockout cells exhibited impaired global protein synthesis and reduced growth. Our data highlight the significance of the tRNA: m2G6/7 modification and pave a way for further studies of the role of m2G in sperm tRNA derived fragments.
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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.