ArticleMolecular biology and evolution2021
Evolution of Methyltransferase-Like (METTL) Proteins in Metazoa: A Complex Gene Family Involved in Epitranscriptomic Regulation and Other Epigenetic Processes.
Article in Molecular biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- METTL17 promotes gastric cancer progression via inhibiting glycogen synthase kinase-3β to activate Wnt/β-catenin signaling.Translational cancer research · 2026Article
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- METTL7A inhibits progression of colorectal cancer through the SREBP1 / FDFT1 / SQLE / CYP51A1 / cholesterol metabolic pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Epitranscriptomics as a Candidate Universal Modulator of Dormancy Transitions.Ecology and evolution · 2026Review
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- Systemic control of HNF1B-driven redox homeostasis by N6-adenosine methylation.Nucleic acids research · 2026Article
- Organophosphate Flame Retardants Disrupt Autism-Relevant Gene Networks Across Development: A Cross-Species Multi-Omics Study.Environmental research · 2025Article
- Elucidating the genetic architecture of migratory timing in a songbird migrant, the great reed warbler, Acrocephalus arundinaceus.Biology open · 2025Article
- The VCPKMT-VCP-HDAC1 axis inhibits colorectal cancer by conferring sensitivity to ferroptosis.Cancer cell international · 2025Article
- Therapeutic Targeting of Protein Lysine and Arginine Methyltransferases: Principles and Strategies for Inhibitor Design.International journal of molecular sciences · 2025Review
- Emerging Orchestrator of Ecological Adaptation: mMolecular ecology · 2025Review
- METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC.Cell death discovery · 2025Article
- Sex-biased gene expression precedes sexual dimorphism in the agonadal annelid Platynereis dumerilii.Development (Cambridge, England) · 2025Article
- Potential prognostic and predictive biomarkers: METTL5, METTL7A, and METTL7B expression in gastrointestinal cancers.Molecular biology reports · 2025Article
- N6-adenosine-methyltransferase MTA70-like participates antiviral responses inFrontiers in microbiology · 2025Article
- Article
- METTL protein family: focusing on the occurrence, progression and treatment of cancer.Biomarker research · 2024Review
- Genome-wide analysis of histone modifications can contribute to the identification of candidate cis-regulatory regions in the threespine stickleback fish.BMC genomics · 2024Article
- Sex-biased gene expression precedes sexual dimorphism in the agonadal annelidbioRxiv : the preprint server for biology · 2024Article
- Mitochondrial RNA modification-based signature to predict prognosis of lower grade glioma: a multi-omics exploration and verification study.Scientific reports · 2024Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The methyltransferase-like (METTL) proteins constitute a family of seven-beta-strand methyltransferases with S-adenosyl methionine-binding domains that modify DNA, RNA, and proteins. Methylation by METTL proteins contributes to the epigenetic, and in the case of RNA modifications, epitranscriptomic regulation of a variety of biological processes. Despite their functional importance, most investigations of the substrates and functions of METTLs within metazoans have been restricted to model vertebrate taxa. In the present work, we explore the evolutionary mechanisms driving the diversification and functional differentiation of 33 individual METTL proteins across Metazoa. Our results show that METTLs are nearly ubiquitous across the animal kingdom, with most having arisen early in metazoan evolution (i.e., occur in basal metazoan phyla). Individual METTL lineages each originated from single independent ancestors, constituting monophyletic clades, which suggests that each METTL was subject to strong selective constraints driving its structural and/or functional specialization. Interestingly, a similar process did not extend to the differentiation of nucleoside-modifying and protein-modifying METTLs (i.e., each METTL type did not form a unique monophyletic clade). The members of these two types of METTLs also exhibited differences in their rates of evolution. Overall, we provide evidence that the long-term evolution of METTL family members was driven by strong purifying selection, which in combination with adaptive selection episodes, led to the functional specialization of individual METTL lineages. This work contributes useful information regarding the evolution of a gene family that fulfills a variety of epigenetic functions, and can have profound influences on molecular processes and phenotypic traits.
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