Extensive translation of circular RNAs driven by N6-methyladenosine

被引：0

作者：

Yun Yang

Xiaojuan Fan

Miaowei Mao

Xiaowei Song

Ping Wu

Yang Zhang

Yongfeng Jin

Yi Yang

Ling-Ling Chen

Yang Wang

Catherine CL Wong

Xinshu Xiao

Zefeng Wang

机构：

[1] Institute of Biochemistry,Department of Integrative Biology and Physiology and the Molecular Biology Institute

[2] College of Life Sciences,Department of Pharmacology

[3] Zhejiang University at Zijingang,undefined

[4] Zhejiang,undefined

[5] CAS Key Lab for Computational Biology,undefined

[6] CAS Center for Excellence in Molecular Cell Science,undefined

[7] CAS-MPG Partner Institute for Computational Biology,undefined

[8] Shanghai Institute for Biological Sciences,undefined

[9] Chinese Academy of Sciences,undefined

[10] UCLA,undefined

[11] University of North Carolina at Chapel Hill,undefined

[12] Synthetic Biology and Biotechnology Laboratory,undefined

[13] State Key Laboratory of Bioreactor Engineering,undefined

[14] School of Pharmacy,undefined

[15] East China University of Science and Technology,undefined

[16] National Center for Protein Science,undefined

[17] Institute of Biochemistry and Cell Biology,undefined

[18] Shanghai Institutes for Biological Sciences,undefined

[19] Chinese Academy of Sciences,undefined

[20] Shanghai Science Research Center,undefined

[21] Chinese Academy of Sciences,undefined

[22] Institute of Biochemistry and Cell Biology,undefined

[23] Shanghai Institute for Biological Sciences,undefined

[24] Chinese Academy of Sciences,undefined

[25] Institute of Cancer Stem Cell,undefined

[26] Dalian Medical University,undefined

来源：

Cell Research | 2017年 / 27卷

关键词：

-methyladenosine; circular RNA; cap-independent translation; eIF4G2;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N6-methyladenosine (m6A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m6A motifs are enriched in circRNAs and a single m6A site is sufficient to drive translation initiation. This m6A-driven translation requires initiation factor eIF4G2 and m6A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m6A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress.

引用

页码：626 / 641

页数：15

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