ArticleMolecular and cellular biology2010
Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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152 citing papers in PubMed, 239 citations in OpenAlex.
- URMylation Signaling Pathway in Cancer: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Elp3 uses a conserved molecular tunnel to transport acetate between distant active sites and catalyze tRNA wobble base modification.Nature communications · 2026Article
- TRMT112 drives a tumor growth and metastasis-promoting program in triple-negative breast cancer.Cell death and differentiation · 2026Article
- Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5.Nature chemical biology · 2026Article
- The Interaction Between Iron and Selenium Affects Ferroptosis in Colorectal Cancer.International journal of molecular sciences · 2026Review
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Genetics of selenoproteins and selenoprotein metabolism - An overview of current concepts and emerging aspects.Redox biology · 2026Review
- Coronaviruses reprogram the tRNA epitranscriptome to favor viral protein expression.Nature communications · 2026Article
- tRNA modifications: greasing the wheels of translation and beyond.RNA biology · 2025Review
- ALKBH8-mediated codon-specific translation promotes colorectal tumorigenesis.Nature communications · 2025Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Structural Impact of 3-methylcytosine Modification on the Anticodon Stem-loop of a Neuronally-enriched Arginine tRNA.Journal of molecular biology · 2025Article
- Recharacterization of the Tumor Suppressive Mechanism of RSL3 Identifies the Selenoproteome as a Druggable Pathway in Colorectal Cancer.Cancer research · 2025Article
- Review
- Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer.European journal of medical research · 2025Review
- Transfer RNA acetylation regulates in vivo mammalian stress signaling.Science advances · 2025Article
- Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis.Nature cancer · 2024Article
- Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
- tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.Nucleic acids research · 2024Review
92 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uridines in the wobble position of tRNA are almost invariably modified. Modifications can increase the efficiency of codon reading, but they also prevent mistranslation by limiting wobbling. In mammals, several tRNAs have 5-methoxycarbonylmethyluridine (mcm5U) or derivatives thereof in the wobble position. Through analysis of tRNA from Alkbh8-/- mice, we show here that ALKBH8 is a tRNA methyltransferase required for the final step in the biogenesis of mcm5U. We also demonstrate that the interaction of ALKBH8 with a small accessory protein, TRM112, is required to form a functional tRNA methyltransferase. Furthermore, prior ALKBH8-mediated methylation is a prerequisite for the thiolation and 2'-O-ribose methylation that form 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) and 5-methoxycarbonylmethyl-2'-O-methyluridine (mcm5Um), respectively. Despite the complete loss of all of these uridine modifications, Alkbh8-/- mice appear normal. However, the selenocysteine-specific tRNA (tRNASec) is aberrantly modified in the Alkbh8-/- mice, and for the selenoprotein Gpx1, we indeed observed reduced recoding of the UGA stop codon to selenocysteine.
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