ArticleNucleic acids research2020
METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 109 citations in OpenAlex.
- Epigenetic regulation of humoral immunity: molecular mechanisms, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- It takes two to tango: the intersection of deubiquitinases and mMolecular cancer · 2026Review
- METTL4 enhances GLI1 translation through mJournal of advanced research · 2026Article
- Role of the m6A methyltransferase Mettl16 in Drosophila development.PLoS genetics · 2026Article
- Engineering Bisubstrates to Target mChemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- FTO separation-of-function mutations alter mbioRxiv : the preprint server for biology · 2026Article
- Genome-Wide Identification and Expression Analysis of mBiology · 2026Article
- Review
- m6AConquer: a consistently quantified and orthogonally validated database for the N6-methyladenosine (m6A) epitranscriptome.Nucleic acids research · 2026Article
- Recent advances in m6A RNA modification in hepatocellular carcinoma: from mechanisms to therapeutic potential.Frontiers in molecular biosciences · 2026Review
- RNA methylation in autoimmune rheumatic diseases: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- METTL4 regulates synaptic UCP2 N6-adenosine methylation to mediate pain hypersensitivity in female mice.Cellular and molecular life sciences : CMLS · 2025Article
- RNA modifications in health and disease: from mechanistic insights to therapeutic applications.Precision clinical medicine · 2025Review
- RNA modifications, alternative splicing and circular RNA landscape in the mouse brain: inosine and beyond.Scientific reports · 2025Article
- Review
- N6-adenosine methyltransferase METTL4 is a potential prognostic biomarker and associates with cell cycle regulation and immune infiltration in glioma.Translational cancer research · 2025Article
- Mechanism for the substrate recognition by a eukaryotic DNA NNature communications · 2025Article
- Multimodal zero-shot learning of previously unseen epitranscriptomes from RNA-seq data.Briefings in bioinformatics · 2025Article
- The importance of physiological and disease contexts in capturing mRNA modifications.Nature structural & molecular biology · 2025Review
- Correlation of METTL4 genetic variants and severe pneumonia pediatric patients in Southern China.BMC genomic data · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N 6-methylation of 2'-O-methyladenosine (Am) in RNA occurs in eukaryotic cells to generate N6,2'-O-dimethyladenosine (m6Am). Identification of the methyltransferase responsible for m6Am catalysis has accelerated studies on the function of m6Am in RNA processing. While m6Am is generally found in the first transcribed nucleotide of mRNAs, the modification is also found internally within U2 snRNA. However, the writer required for catalyzing internal m6Am formation had remained elusive. By sequencing transcriptome-wide RNA methylation at single-base-resolution, we identified human METTL4 as the writer that directly methylates Am at U2 snRNA position 30 into m6Am. We found that METTL4 localizes to the nucleus and its conserved methyltransferase catalytic site is required for U2 snRNA methylation. By sequencing human cells with overexpressed Mettl4, we determined METTL4's in vivo target RNA motif specificity. In the absence of Mettl4 in human cells, U2 snRNA lacks m6Am thereby affecting a subset of splicing events that exhibit specific features such as 3' splice-site weakness and an increase in exon inclusion. These findings suggest that METTL4 methylation of U2 snRNA regulates splicing of specific pre-mRNA transcripts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.