N6-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics

• Published in: Nature structural & molecular biology Vol. 23; no. 2; pp. 110 - 115
• Main Authors: Choi, Junhong, Ieong, Ka-Weng, Demirci, Hasan, Chen, Jin, Petrov, Alexey, Prabhakar, Arjun, O'Leary, Seán E, Dominissini, Dan, Rechavi, Gideon, Soltis, S Michael, Ehrenberg, Måns, Puglisi, Joseph D
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2016; Nature Publishing Group
• Subjects: 631/337/1645/2570; 631/337/2265; 631/337/574; Analysis; Biochemistry; Biological Microscopy; Crystallography; E coli; Life Sciences; Membrane Biology; Methylation; Protein Structure; Ribonucleic acid; RNA; X-rays
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.3148

Methylation of adenosine within mRNA coding regions delays tRNA accommodation during translation and thus changes translation dynamics, which might influence protein folding. N 6 -methylation of adenosine (forming m 6 A) is the most abundant post-transcriptional modification within the coding region of mRNA, but its role during translation remains unknown. Here, we used bulk kinetic and single-molecule methods to probe the effect of m 6 A in mRNA decoding. Although m 6 A base-pairs with uridine during decoding, as shown by X-ray crystallographic analyses of Thermus thermophilus ribosomal complexes, our measurements in an Escherichia coli translation system revealed that m 6 A modification of mRNA acts as a barrier to tRNA accommodation and translation elongation. The interaction between an m 6 A-modified codon and cognate tRNA echoes the interaction between a near-cognate codon and tRNA, because delay in tRNA accommodation depends on the position and context of m 6 A within codons and on the accuracy level of translation. Overall, our results demonstrate that chemical modification of mRNA can change translational dynamics.