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Nat Struct Mol Biol. 2016 Feb;23(2):110-5. doi: 10.1038/nsmb.3148. Epub 2016 Jan 11.

N(6)-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics.

Author information

1
Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA.
2
Department of Applied Physics, Stanford University, Stanford, California, USA.
3
Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden.
4
Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
5
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
6
Program in Biophysics, Stanford University, Stanford, California, USA.
7
Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
8
Israel &Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

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.

PMID:
26751643
PMCID:
PMC4826618
DOI:
10.1038/nsmb.3148
[Indexed for MEDLINE]
Free PMC Article

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