ArticleNucleic acids research2022
Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- Mettl8 Regulates Hippocampal Neural Stem Cell Proliferation and Neurogenesis via mTOR/4E-BP1 Signaling.CNS neuroscience & therapeutics · 2026Article
- RNA methylation in autoimmune rheumatic diseases: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Article
- Targeting tRNA methyltransferases: from molecular mechanisms to drug discovery.Science China. Life sciences · 2025Review
- Transcriptome-wide mapping of N3-methylcytidine modification at single-base resolution.Nucleic acids research · 2025Article
- A genome-wide association study identifies new loci associated with response to SARS-CoV-2 mRNA-1273 vaccine in a cohort of healthy healthcare workers.Frontiers in immunology · 2025Article
- NImmunity, inflammation and disease · 2024Review
- tRNA and tsRNA: From Heterogeneity to Multifaceted Regulators.Biomolecules · 2024Review
- Structural basis of tRNA recognition by the mNature structural & molecular biology · 2024Article
- tRNA modifications and tRNA-derived small RNAs: new insights of tRNA in human disease.Cell biology and toxicology · 2024Review
- METTL Family in Healthy and Disease.Molecular biomedicine · 2024Review
- ADATs: roles in tRNA editing and relevance to disease.Acta biochimica et biophysica Sinica · 2024Review
- Mitochondrial RNA modification-based signature to predict prognosis of lower grade glioma: a multi-omics exploration and verification study.Scientific reports · 2024Article
- METTL8 links mt-tRNA mCell death & disease · 2024Article
- Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression.Nucleic acids research · 2024Article
- The impact of tRNA modifications on translation in cancer: identifying novel therapeutic avenues.NAR cancer · 2024Review
- Protein-Protein Interactions of Seryl-tRNA Synthetases with Emphasis on Human Counterparts and Their Connection to Health and Disease.Life (Basel, Switzerland) · 2024Review
- Research Advances on Deafness Genes Associated with Mitochondrial tRNA-37 Modifications.The journal of international advanced otology · 2023Review
- Methyltransferase-like proteins in cancer biology and potential therapeutic targeting.Journal of hematology & oncology · 2023Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
METTL8 has recently been identified as the methyltransferase catalyzing 3-methylcytidine biogenesis at position 32 (m3C32) of mitochondrial tRNAs. METTL8 also potentially participates in mRNA methylation and R-loop biogenesis. How METTL8 plays multiple roles in distinct cell compartments and catalyzes mitochondrial tRNA m3C formation remain unclear. Here, we discovered that alternative mRNA splicing generated several isoforms of METTL8. One isoform (METTL8-Iso1) was targeted to mitochondria via an N-terminal pre-sequence, while another one (METTL8-Iso4) mainly localized to the nucleolus. METTL8-Iso1-mediated m3C32 modification of human mitochondrial tRNAThr (hmtRNAThr) was not reliant on t6A modification at A37 (t6A37), while that of hmtRNASer(UCN) critically depended on i6A modification at A37 (i6A37). We clarified the hmtRNAThr substrate recognition mechanism, which was obviously different from that of hmtRNASer(UCN), in terms of requiring a G35 determinant. Moreover, SARS2 (mitochondrial seryl-tRNA synthetase) interacted with METTL8-Iso1 in an RNA-independent manner and modestly accelerated m3C modification activity. We further elucidated how nonsubstrate tRNAs in human mitochondria were efficiently discriminated by METTL8-Iso1. In summary, our results established the expression pattern of METTL8, clarified the molecular basis for m3C32 modification by METTL8-Iso1 and provided the rationale for the involvement of METTL8 in tRNA modification, mRNA methylation or R-loop biogenesis.
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