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

Junhong Choi, Ka Weng Ieong, Hasan Demirci, Jin Chen, Alexey Petrov, Arjun Prabhakar, Seán E. O'Leary, Dan Dominissini, Gideon Rechavi, S. Michael Soltis, Mans Ehrenberg, Joseph D. Puglisi

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

N6 -methylation of adenosine (forming m6A) 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 m6A in mRNA decoding. Although m6A 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 m6A modification of mRNA acts as a barrier to tRNA accommodation and translation elongation. The interaction between an m6A-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 m6A within codons and on the accuracy level of translation. Overall, our results demonstrate that chemical modification of mRNA can change translational dynamics.

Original languageEnglish (US)
Pages (from-to)110-115
Number of pages6
JournalNature Structural and Molecular Biology
Volume23
Issue number2
DOIs
StatePublished - Feb 3 2016
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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