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PMID: 26751643 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Nature structural & molecular biology ·Vol. 23 ·No. 2 ·2016-02-00 ·Pages 110-5

Choi J, Ieong KW, Demirci H, Chen J, Petrov A, Prabhakar A, O'Leary SE, Dominissini D, Rechavi G, Soltis SM, Ehrenberg M, Puglisi JD

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.

MeSH Terms
Adenosine/analogs & derivatives,analysis,genetics Codon Crystallography, X-Ray Escherichia coli/chemistry,genetics Protein Biosynthesis RNA, Bacterial/chemistry,genetics RNA, Messenger/chemistry,genetics RNA, Transfer/chemistry,genetics Thermus thermophilus/chemistry,genetics
Chemicals
Codon RNA, Bacterial RNA, Messenger RNA, Transfer N-methyladenosine Adenosine
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Choi Junhong ORCID
Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA. | Department of Applied Physics, Stanford University, Stanford, California, USA.
Ieong Ka-Weng
Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Demirci Hasan ORCID
Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, California, USA. | Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
Chen Jin
Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA. | Department of Applied Physics, Stanford University, Stanford, California, USA.
Petrov Alexey
Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA.
Prabhakar Arjun
Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA. | Program in Biophysics, Stanford University, Stanford, California, USA.
O'Leary Seán E
Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA.
Dominissini Dan
Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Rechavi Gideon
Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel. | Israel &Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Soltis S Michael
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
Ehrenberg Måns
Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Puglisi Joseph D
Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA.
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.3148
Published
2016-02-00
Epub
2016-00-11
Pages
110-5
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC4826618
Subset
IM
Grants
NIGMS NIH HHS · GM111858 · United States
NIGMS NIH HHS · R00 GM111858 · United States
NIGMS NIH HHS · R01 GM099687 · United States
NIGMS NIH HHS · T32 GM008294 · United States
NIGMS NIH HHS · R01 GM051266 · United States
NIGMS NIH HHS · GM51266 · United States
NIGMS NIH HHS · GM099687 · United States
NIGMS NIH HHS · K99 GM111858 · United States
External Links
PubMed source DOI: 10.1038/nsmb.3148 PMC Full Text View journal details
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