Details

Autor(en) / Beteiligte

• Jain, Sakshi
• Koziej, Lukasz
• Poulis, Panagiotis
• Kaczmarczyk, Igor
• Gaik, Monika
• Rawski, Michal
• Ranjan, Namit
• Glatt, Sebastian
• Rodnina, Marina V

Titel

Modulation of translational decoding by m6A modification of mRNA

Ist Teil von

• Nature communications, 2023-08, Vol.14 (1), p.4784-4784, Article 4784

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.