ArticleNucleic acids research2021
Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function.
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 41 papers.
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Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- METTL18 is Required for Developmental, Metabolic, and Endocrine Regulation of Mammalian Growth.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- METTL18-catalyzed histidine methylation of YTHDF2 promotes mRNA stability.Science China. Life sciences · 2026Article
- CYP2C19 Genotype is Associated with Citalopram Treatment Outcomes in a Real-World Setting.Clinical pharmacology and therapeutics · 2026Article
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- Orphan Enzymes in the Mammalian L-Fucose Degradation Pathway.Biomolecules · 2026Review
- Substrate selectivity of human histidine methyltransferase METTL9.Protein science : a publication of the Protein Society · 2026Article
- Backbone Thioamidation of a Ribosomal Subunit Protein in Pseudomonadota.Biochemistry · 2026Article
- METTL18 ensures pancreatic function by maintaining proper translation and proteostasis.Molecular metabolism · 2026Article
- The Protein Histidine Methyltransferase METTL9-From Mechanism to Biological Function.Life (Basel, Switzerland) · 2026Review
- Ubc9-Mediated SUMOylation of RPL3, an Unappreciated Mechanism against Hepatocyte Senescence by Repressing the DHX9-p16 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- METTL9 mediated N1-Histidine methylation of SLC39A7 confers ferroptosis resistance and inhibits adipogenic differentiation in mesenchymal stem cells.Molecular medicine (Cambridge, Mass.) · 2025Article
- Built differently or defective: can RNA exosomopathies cause ribosome heterogeneity?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM.Science China. Life sciences · 2025Article
- Visualizing the modification landscape of the human 60S ribosomal subunit at close to atomic resolution.Nucleic acids research · 2025Article
- Article
- Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.Nucleic acids research · 2024Review
- Orthogonal Translation for Site-Specific Installation of Post-translational Modifications.Chemical reviews · 2024Review
- METTL18 functions as a Phenotypic Regulator in Src-Dependent Oncogenic Responses of HER2-Negative Breast Cancer.International journal of biological sciences · 2024Article
- Znf598-mediated Rps10/eS10 ubiquitination contributes to the ribosome ubiquitination dynamics during zebrafish development.RNA (New York, N.Y.) · 2023Article
- Methyltransferase-like proteins in cancer biology and potential therapeutic targeting.Journal of hematology & oncology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein methylation occurs primarily on lysine and arginine, but also on some other residues, such as histidine. METTL18 is the last uncharacterized member of a group of human methyltransferases (MTases) that mainly exert lysine methylation, and here we set out to elucidate its function. We found METTL18 to be a nuclear protein that contains a functional nuclear localization signal and accumulates in nucleoli. Recombinant METTL18 methylated a single protein in nuclear extracts and in isolated ribosomes from METTL18 knockout (KO) cells, identified as 60S ribosomal protein L3 (RPL3). We also performed an RPL3 interactomics screen and identified METTL18 as the most significantly enriched MTase. We found that His-245 in RPL3 carries a 3-methylhistidine (3MH; τ-methylhistidine) modification, which was absent in METTL18 KO cells. In addition, both recombinant and endogenous METTL18 were found to be automethylated at His-154, thus further corroborating METTL18 as a histidine-specific MTase. Finally, METTL18 KO cells displayed altered pre-rRNA processing, decreased polysome formation and codon-specific changes in mRNA translation, indicating that METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function. In conclusion, we have here established METTL18 as the second human histidine-specific protein MTase, and demonstrated its functional relevance.
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