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

被引：201

作者：

Choi, Junhong ^{[1
,2
]}

Ieong, Ka-Weng ^{[3
]}

Demirci, Hasan ^{[4
,5
]}

Chen, Jin ^{[1
,2
]}

Petrov, Alexey ^{[1
]}

Prabhakar, Arjun ^{[1
,6
]}

O'Leary, Sean E. ^{[1
]}

Dominissini, Dan ^{[7
,9
]}

Rechavi, Gideon ^{[7
,8
]}

Soltis, S. Michael ^{[5
]}

Ehrenberg, Mans ^{[3
]}

Puglisi, Joseph D. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA

[3] Uppsala Univ, Biomed Ctr, Dept Cell & Mol Biol, Uppsala, Sweden

[4] SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA USA

[5] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA USA

[6] Stanford Univ, Program Biophys, Stanford, CA 94305 USA

[7] Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel

[8] Tel Aviv Univ, Israel & Sackler Sch Med, IL-69978 Tel Aviv, Israel

[9] Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2016年 / 23卷 / 02期

基金：

美国国家卫生研究院; 以色列科学基金会; 瑞典研究理事会;

关键词：

METHYLATION; RIBOSOME; M(6)A; WIDESPREAD; REVEALS; SYSTEM;

D O I：

10.1038/nsmb.3148

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：110 / +

页数：8

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