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N-6-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics
Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.;Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA USA.;SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA USA..
Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.;Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA..
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2016 (English)In: Nature Structural & Molecular Biology, ISSN 1545-9993, E-ISSN 1545-9985, Vol. 23, no 2, 110-+ p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 23, no 2, 110-+ p.
National Category
Cell and Molecular Biology
URN: urn:nbn:se:uu:diva-277998DOI: 10.1038/nsmb.3148ISI: 000369220800006PubMedID: 26751643OAI: oai:DiVA.org:uu-277998DiVA: diva2:906074
NIH (National Institute of Health), GM51266NIH (National Institute of Health), GM099687Knut and Alice Wallenberg FoundationSwedish Research CouncilNIH (National Institute of Health), GM111858
Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2016-02-23Bibliographically approved

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