학술논문
Modulation of translational decoding by m6 A modification of mRNA
Document Type
Original Paper
Author
Source
Nature Communications. 14(1)
Subject
Language
English
ISSN
2041-1723
Abstract
N6 -methyladenosine (m6 A) is an abundant, dynamic mRNA modification that regulates key steps of cellular mRNA metabolism. m6 A in the mRNA coding regions inhibits translation elongation. Here, we show how m6 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 m6 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. m6 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.
m6 A is an mRNA modification that slows down translation elongation. Here, Jain et al. show that m6 A delays decoding and increases tRNA drop-off from the ribosome by favoring alternative codon conformations that are rejected by the ribosome.
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