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Modulation of translational decoding by m6A modification of mRNA

Author

Listed:
  • Sakshi Jain

    (Max Planck Institute for Multidisciplinary Sciences)

  • Lukasz Koziej

    (Jagiellonian University)

  • Panagiotis Poulis

    (Max Planck Institute for Multidisciplinary Sciences)

  • Igor Kaczmarczyk

    (Jagiellonian University
    Jagiellonian University)

  • Monika Gaik

    (Jagiellonian University)

  • Michal Rawski

    (Jagiellonian University
    Jagiellonian University)

  • Namit Ranjan

    (Max Planck Institute for Multidisciplinary Sciences)

  • Sebastian Glatt

    (Jagiellonian University)

  • Marina V. Rodnina

    (Max Planck Institute for Multidisciplinary Sciences)

Abstract

N6-methyladenosine (m6A) is an abundant, dynamic mRNA modification that regulates key steps of cellular mRNA metabolism. m6A in the mRNA coding regions inhibits translation elongation. Here, we show how m6A modulates decoding in the bacterial translation system using a combination of rapid kinetics, smFRET and single-particle cryo-EM. We show that, while the modification does not impair the initial binding of aminoacyl-tRNA to the ribosome, in the presence of m6A fewer ribosomes complete the decoding process due to the lower stability of the complexes and enhanced tRNA drop-off. The mRNA codon adopts a π-stacked codon conformation that is remodeled upon aminoacyl-tRNA binding. m6A does not exclude canonical codon-anticodon geometry, but favors alternative more dynamic conformations that are rejected by the ribosome. These results highlight how modifications outside the Watson-Crick edge can still interfere with codon-anticodon base pairing and complex recognition by the ribosome, thereby modulating the translational efficiency of modified mRNAs.

Suggested Citation

  • Sakshi Jain & Lukasz Koziej & Panagiotis Poulis & Igor Kaczmarczyk & Monika Gaik & Michal Rawski & Namit Ranjan & Sebastian Glatt & Marina V. Rodnina, 2023. "Modulation of translational decoding by m6A modification of mRNA," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40422-7
    DOI: 10.1038/s41467-023-40422-7
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