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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., et al. (2023). Modulation of translational decoding by m6A modification of mRNA. Nature Communications, 14: 4784. doi:10.1038/s41467-023-40422-7.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000D-A574-6 Version Permalink: https://hdl.handle.net/21.11116/0000-000E-09DC-1
Genre: Journal Article
Other : Modulation of translational decoding by m6A modification of mRNA
Other : Modulation of translational decoding by m(6)A modification of mRNA

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 Creators:
Jain, Sakshi1, Author           
Koziej, Lukasz, Author
Poulis, Panagiotis1, Author           
Kaczmarczyk, Igor, Author
Gaik, Monika, Author
Rawski, Michal, Author
Ranjan, Namit1, Author           
Glatt, Sebastian, Author
Rodnina, Marina V.1, Author                 
Affiliations:
1Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350156              

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 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.

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Language(s): eng - English
 Dates: 2023-08-08
 Publication Status: Published online
 Pages: -
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-023-40422-7
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Project name : The work was supported by the German Research Council (Deutsche Forschungsgemeinschaft) (Priority Programme SPP1784 to N.R. and M.V.R., Germany’s Excellence Strategy - EXC 2067/1- 390729940 and Leibniz Prize to M.V.R.) and the European Research Council (ERC) (grant agreement No 101001394- tRNAslation to S.G.). We thank the MCB structural biology core facility (supported by the TEAM TECH CORE FACILITY/2017-4/6 grant from Foundation for Polish Science, S.G.) for providing instruments and support. This publication was developed under the provision of the Polish Ministry of Education and Science project: “Support for research and development with the use of research infrastructure of the National Synchrotron Radiation Centre SOLARIS” under contract nr 1/SOL/2021/2. We acknowledge SOLARIS Centre for the access to the Krios microscope, where the measurements were performed. This research was supported in part by PLGrid Infrastructure (Academic Computer Centre Cyfronet AGH).
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Funding organization : -
Project name : tRNAslation
Grant ID : 101001394
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 14 Sequence Number: 4784 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723