ArticleNucleic acids research2017
The novel lysine specific methyltransferase METTL21B affects mRNA translation through inducible and dynamic methylation of Lys-165 in human eukaryotic elongation factor 1 alpha (eEF1A).
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 86 citations in OpenAlex.
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 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
- Predicting the structural impact of human alternative splicing.Genome biology · 2025Article
- The proteomic landscape of diffuse midline glioma highlights the therapeutic potential of non-histone protein methyltransferases.Neuro-oncology · 2025Article
- Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.Nucleic acids research · 2024Review
- Genome-scale exon perturbation screens uncover exons critical for cell fitness.Molecular cell · 2024Article
- Profiling the compendium of changes in Saccharomyces cerevisiae due to mutations that alter availability of the main methyl donor S-Adenosylmethionine.G3 (Bethesda, Md.) · 2024Article
- Genome-wide analysis of the soybeanFrontiers in plant science · 2024Article
- Phosphorylated Adapter RNA Export Protein Is Methylated at Lys 381 by an Methyltransferase-like 21C (METTL21C).International journal of molecular sciences · 2023Article
- Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain.Cell reports. Medicine · 2023Article
- Endothelial RIPK1 protects artery bypass graft against arteriosclerosis by regulating SMC growth.Science advances · 2023Article
- Roles and regulatory mechanisms of KIN17 in cancers (Review).Oncology letters · 2023Review
- METTL13 facilitates cell growth and metastasis in gastric cancer via an eEF1A/HN1L positive feedback circuit.Journal of cell communication and signaling · 2023Article
- Article
- METTLing in Stem Cell and Cancer Biology.Stem cell reviews and reports · 2023Review
- Moonlighting translation factors: multifunctionality drives diverse gene regulation.Trends in cell biology · 2022Review
- Crosstalk of Epigenetic and Metabolic Signaling Underpinning Glioblastoma Pathogenesis.Cancers · 2022Review
- Protein methylation in mitochondria.The Journal of biological chemistry · 2022Review
- METTL21A, a Non-Histone Methyltransferase, Is Dispensable for Spermatogenesis and Male Fertility in Mice.International journal of molecular sciences · 2022Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysine methylation is abundant on histone proteins, representing a dynamic regulator of chromatin state and gene activity, but is also frequent on many non-histone proteins, including eukaryotic elongation factor 1 alpha (eEF1A). However, the functional significance of eEF1A methylation remains obscure and it has remained unclear whether eEF1A methylation is dynamic and subject to active regulation. We here demonstrate, using a wide range of in vitro and in vivo approaches, that the previously uncharacterized human methyltransferase METTL21B specifically targets Lys-165 in eEF1A in an aminoacyl-tRNA- and GTP-dependent manner. Interestingly, METTL21B-mediated eEF1A methylation showed strong variation across different tissues and cell lines, and was induced by altering growth conditions or by treatment with certain ER-stress-inducing drugs, concomitant with an increase in METTL21B gene expression. Moreover, genetic ablation of METTL21B function in mammalian cells caused substantial alterations in mRNA translation, as measured by ribosomal profiling. A non-canonical function for eEF1A in organization of the cellular cytoskeleton has been reported, and interestingly, METTL21B accumulated in centrosomes, in addition to the expected cytosolic localization. In summary, the present study identifies METTL21B as the enzyme responsible for methylation of eEF1A on Lys-165 and shows that this modification is dynamic, inducible and likely of regulatory importance.
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