최준홍 (Stanford University School of Medicine) | 한빛사논문 > 한빛사

한빛사논문

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Stanford University School of Medicine

Nat. Struct. Mol. Biol., Published online 11 January 2016 | doi:10.1038/nsmb.3148 N6-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics

Abstract

Junhong Choi^1,2, Ka-Weng Ieong³, Hasan Demirci^4,5, Jin Chen^1,2, Alexey Petrov¹, Arjun Prabhakar^1,6, Sean E O’Leary¹, Dan Dominissini^7,9, Gideon Rechavi^7,8, S Michael Soltis⁵, Mans Ehrenberg³ & Joseph D Puglisi¹

¹Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA. ²Department of Applied Physics, Stanford University, Stanford, California, USA. ³Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. ⁴Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, California, USA. ⁵Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, USA. ⁶Program in Biophysics, Stanford University, Stanford, California, USA. ⁷Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel. ⁸Israel & Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 9Present address: Department of Chemistry, University of Chicago, Chicago, Illinois, USA.

Correspondence to : Joseph D Puglisi

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.

논문정보

형식Research article
게재일2016년 01월 (BRIC 등록일 2016-01-20)
연구진국외 연구진
분야 생명과학 > 분자생물학

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