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Updated: Jul 19, 2025

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

Published on: December 5, 2016

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Modulation of translational decoding by m6A modification of mRNA

Sakshi Jain1, Lukasz Koziej2, Panagiotis Poulis1

  • 1Max Planck Institute for Multidisciplinary Sciences, Göttingen, 37077, Germany.

Nature Communications
|August 8, 2023
PubMed

Insights

N6-methyladenosine (m6A) modifies mRNA, impacting bacterial translation. This m6A modification hinders ribosome decoding by destabilizing complexes and increasing tRNA drop-off, affecting protein synthesis.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • N6-methyladenosine (m6A) is a prevalent mRNA modification influencing mRNA metabolism.
  • m6A within mRNA coding regions is known to inhibit translation elongation.

Purpose of the Study:

  • To elucidate the mechanism by which m6A modulates decoding in bacterial translation systems.
  • To investigate the impact of m6A on ribosome-mRNA-tRNA interactions during translation.

Main Methods:

  • Utilized a combination of rapid kinetics, single-molecule Förster Resonance Energy Transfer (smFRET), and single-particle cryo-electron microscopy (cryo-EM).
  • Analyzed the stability of ribosome complexes and tRNA drop-off rates in the presence and absence of m6A.
  • Examined mRNA codon conformation and its remodeling upon aminoacyl-tRNA binding.

Main Results:

  • m6A does not impede the initial binding of aminoacyl-tRNA to the ribosome.
  • Fewer ribosomes successfully complete decoding in the presence of m6A due to reduced complex stability and increased tRNA drop-off.
  • m6A favors dynamic mRNA codon conformations that are less compatible with canonical codon-anticodon pairing and are rejected by the ribosome.

Conclusions:

  • m6A modifications, even outside the direct codon-anticodon interaction site, can interfere with base pairing and ribosome recognition.
  • These interactions modulate translational efficiency by affecting decoding fidelity and complex stability.
  • The study reveals a novel mechanism by which mRNA modifications regulate gene expression at the translational level.

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