Modulation of translational decoding by m6A modification of mRNA
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Modulation of translational decoding by m6A modification of mRNA
Jain, S.; Koziej, L.; Poulis, P.; Kaczmarczyk, I.; Gaik, M.; Rawski, M. & Ranjan, N. et al. (2023)
Nature Communications, 14(1). DOI: https://doi.org/10.1038/s41467-023-40422-7
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Details
- Authors
- Jain, Sakshi; Koziej, Lukasz; Poulis, Panagiotis; Kaczmarczyk, Igor; Gaik, Monika; Rawski, Michal; Ranjan, Namit; Glatt, Sebastian; Rodnina, Marina V.
- Abstract
- N 6 -methyladenosine (m 6 A) is an abundant, dynamic mRNA modification that regulates key steps of cellular mRNA metabolism. m 6 A in the mRNA coding regions inhibits translation elongation. Here, we show how m 6 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 6 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 6 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.
- Issue Date
- 2023
- Journal
- Nature Communications
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Rodnina
- eISSN
- 2041-1723
- Language
- English