Modulation of translational decoding by m6A modification of mRNA
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40422-7 |
| _version_ | 1797558717236903936 |
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| author | Sakshi Jain Lukasz Koziej Panagiotis Poulis Igor Kaczmarczyk Monika Gaik Michal Rawski Namit Ranjan Sebastian Glatt Marina V. Rodnina |
| author_facet | Sakshi Jain Lukasz Koziej Panagiotis Poulis Igor Kaczmarczyk Monika Gaik Michal Rawski Namit Ranjan Sebastian Glatt Marina V. Rodnina |
| author_sort | Sakshi Jain |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:35:26Z |
| format | Article |
| id | doaj.art-56f48722b7584297a4c65b1c09193dce |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:35:26Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-56f48722b7584297a4c65b1c09193dce2023-11-20T09:52:40ZengNature PortfolioNature Communications2041-17232023-08-0114111310.1038/s41467-023-40422-7Modulation of translational decoding by m6A modification of mRNASakshi Jain0Lukasz Koziej1Panagiotis Poulis2Igor Kaczmarczyk3Monika Gaik4Michal Rawski5Namit Ranjan6Sebastian Glatt7Marina V. Rodnina8Max Planck Institute for Multidisciplinary SciencesMalopolska Centre of Biotechnology, Jagiellonian UniversityMax Planck Institute for Multidisciplinary SciencesMalopolska Centre of Biotechnology, Jagiellonian UniversityMalopolska Centre of Biotechnology, Jagiellonian UniversityMalopolska Centre of Biotechnology, Jagiellonian UniversityMax Planck Institute for Multidisciplinary SciencesMalopolska Centre of Biotechnology, Jagiellonian UniversityMax Planck Institute for Multidisciplinary SciencesAbstract 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.https://doi.org/10.1038/s41467-023-40422-7 |
| spellingShingle | Sakshi Jain Lukasz Koziej Panagiotis Poulis Igor Kaczmarczyk Monika Gaik Michal Rawski Namit Ranjan Sebastian Glatt Marina V. Rodnina Modulation of translational decoding by m6A modification of mRNA Nature Communications |
| title | Modulation of translational decoding by m6A modification of mRNA |
| title_full | Modulation of translational decoding by m6A modification of mRNA |
| title_fullStr | Modulation of translational decoding by m6A modification of mRNA |
| title_full_unstemmed | Modulation of translational decoding by m6A modification of mRNA |
| title_short | Modulation of translational decoding by m6A modification of mRNA |
| title_sort | modulation of translational decoding by m6a modification of mrna |
| url | https://doi.org/10.1038/s41467-023-40422-7 |
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