ArticleNucleic acids research2024
U6 snRNA m6A modification is required for accurate and efficient splicing of C. elegans and human pre-mRNAs.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Deployment of non-canonical splicing in tunicate genomes is mediated by divergent U2AF function and changing m6A modification in U1 and U6 snRNA.Nucleic acids research · 2026Article
- 2'-O-methylation-dependent installation of NNature communications · 2026Article
- Targeting intracellular mRNA mJournal of advanced research · 2026Review
- METTL16 in cancer: Roles and regulatory mechanisms.Genes & diseases · 2026Review
- Widespread intron retention and exon skipping characterise alternative splicing changes in a C. elegans model of spinal muscular atrophy.Human molecular genetics · 2026Article
- Mechanism of alternative splicing of yeast HEH1 through competing 5' splice sites.Nature communications · 2025Article
- Article
- Structures and mechanisms of U6 snRNA mNature communications · 2025Article
- Review
- Peptide Drug: Design and Clinical Applications.MedComm · 2025Review
- The catalytic efficiency of METTL16 affects cellular processes by governing the intracellular S-adenosylmethionine setpoint.Cell reports · 2025Article
- Cryo-EM structure of human TUT1:U6 snRNA complex.Nucleic acids research · 2025Article
- RNA splicing: a split consensus reveals two major 5' splice site classes.Open biology · 2025Review
- Article
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12 authors.
Funding
Abstract
pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing. Here, we show that the conserved U6 snRNA m6A methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing of C. elegans pre-mRNAs. The absence of METT-10 in C. elegans and METTL16 in humans primarily leads to alternative splicing at 5' splice sites with an adenosine at +4 position. In addition, METT-10 is required for splicing of weak 3' cis- and trans-splice sites. We identified a significant overlap between METT-10 and the conserved splicing factor SNRNP27K in regulating 5' splice sites with +4A. Finally, we show that editing endogenous 5' splice site +4A positions to +4U restores splicing to wild-type positions in a mett-10 mutant background, supporting a direct role for U6 snRNA m6A modification in 5' splice site recognition. We conclude that the U6 snRNA m6A modification is important for accurate and efficient pre-mRNA splicing.
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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 Socratic graph.