Modulation of translational decoding by m 6 A modification of mRNA

N -methyladenosine (m A) is an abundant, dynamic mRNA modification that regulates key steps of cellular mRNA metabolism. m A in the mRNA coding regions inhibits translation elongation. Here, we show how m A modulates decoding in the bacterial translation system using a combination of rapid kinetics,...

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Veröffentlicht in:Nature communications 2023-08, Vol.14 (1), p.4784
Hauptverfasser: Jain, Sakshi, Koziej, Lukasz, Poulis, Panagiotis, Kaczmarczyk, Igor, Gaik, Monika, Rawski, Michal, Ranjan, Namit, Glatt, Sebastian, Rodnina, Marina V
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Sprache:eng
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Zusammenfassung:N -methyladenosine (m A) is an abundant, dynamic mRNA modification that regulates key steps of cellular mRNA metabolism. m A in the mRNA coding regions inhibits translation elongation. Here, we show how m A 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 m A 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. m A 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.
ISSN:2041-1723