ArticleNucleic acids research2021
N 6-Methyladenosines in mRNAs reduce the accuracy of codon reading by transfer RNAs and peptide release factors.
Article in Nucleic acids research, 2021. 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, 14 citations in OpenAlex.
- Molecular functions, cellular responses and pathological implications of the RNA modification NNature reviews. Molecular cell biology · 2026Review
- Compendium of RNA modifications for bacterial stress adaptation.Microbiology and molecular biology reviews : MMBR · 2026Review
- Epitranscriptomic control of stress adaptations in Escherichia coli.Nucleic acids research · 2026Article
- m6A modification is incorporated into bacterial mRNA without specific functional benefit.Nucleic acids research · 2025Article
- NMolecular cell · 2024Article
- Modulation of translational decoding by mNature communications · 2023Article
- Whole-cell modeling of E. coli confirms that in vitro tRNA aminoacylation measurements are insufficient to support cell growth and predicts a positive feedback mechanism regulating arginine biosynthesis.Nucleic acids research · 2023Article
- METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL.Blood cancer discovery · 2023Article
- mRNA and tRNA modification states influence ribosome speed and frame maintenance during poly(lysine) peptide synthesis.The Journal of biological chemistry · 2022Article
- An RNA methylation code to regulate protein translation and cell fate.Cell proliferation · 2022Article
- Zero-mode waveguides and nanopore-based sequencing technologies accelerate single-molecule studies.Biophysics and physicobiology · 2022Article
- Sequence determinants as key regulators in gene expression of T cells.Immunological reviews · 2021Review
- The Importance of the Epi-Transcriptome in Translation Fidelity.Non-coding RNA · 2021Review
- Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
We used quench flow to study how N6-methylated adenosines (m6A) affect the accuracy ratio between kcat/Km (i.e. association rate constant (ka) times probability (Pp) of product formation after enzyme-substrate complex formation) for cognate and near-cognate substrate for mRNA reading by tRNAs and peptide release factors 1 and 2 (RFs) during translation with purified Escherichia coli components. We estimated kcat/Km for Glu-tRNAGlu, EF-Tu and GTP forming ternary complex (T3) reading cognate (GAA and Gm6AA) or near-cognate (GAU and Gm6AU) codons. ka decreased 10-fold by m6A introduction in cognate and near-cognate cases alike, while Pp for peptidyl transfer remained unaltered in cognate but increased 10-fold in near-cognate case leading to 10-fold amino acid substitution error increase. We estimated kcat/Km for ester bond hydrolysis of P-site bound peptidyl-tRNA by RF2 reading cognate (UAA and Um6AA) and near-cognate (UAG and Um6AG) stop codons to decrease 6-fold or 3-fold by m6A introduction, respectively. This 6-fold effect on UAA reading was also observed in a single-molecule termination assay. Thus, m6A reduces both sense and stop codon reading accuracy by decreasing cognate significantly more than near-cognate kcat/Km, in contrast to most error inducing agents and mutations, which increase near-cognate at unaltered cognate kcat/Km.
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Registered trials
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