文献类型：期刊文献

中文题名：Extensive translation of circular RNAs driven by N6-methyladenosine

英文题名：Extensive translation of circular RNAs driven by N6-methyladenosine

作者：Yun Yang[1,2,3,4];Xiaojuan Fan[2];Miaowei Mao[4,5];Xiaowei Song[2,4];Ping Wu6,7[1];Yang Zhang[8];Yongfeng Jin[1];Yi Yang[5];Ling-Ling Chen[8];Yang Wang[9];Catherine CL Wong[6,7];Xinshu Xiao[3];Zefeng Wang[2,4]

机构：[1]Institute of Biochemistry, College of Life Sciences, Zhejiang University at Zijingang, Zhejiang, Hangzhou, Zhejiang 310058, China;[2]CAS Key Lab Jot Computational Biology, CAS Center Jor Excellence in Molecular Cell Science, CAS-MPG Partner Institute .for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;[3]Department of Integrative Biology and Physiology and the Molecular Biology Institute, UCLA,Los Angeles,CA 90095,USA;[4]Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;[5]Synthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China;[6]National Center for Protein Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;[7]Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai 201204, China;[8]Institute of Biochemistry and Cell Biology, Shanghai Institute for Biolog- ical Sciences, Chinese Academy of Sciences, Shanghai 200031, China;[9]Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning 116044, China

年份：2017

卷号：27

期号：5

起止页码：626

中文期刊名：Cell Research

外文期刊名：细胞研究（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2017_2018】；PubMed;

语种：英文

中文关键词：N6-methyladenosine; circular RNA; cap-independent translation; elF4G2

外文关键词：N ⁶-methyladenosine；圆形的 RNA；帽子无关的翻译；eIF4G2

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 N%methyladenosine （m6A）, the most abundant base modification of RNA, promotes efficient initiation of protein translation from cir- cRNAs in human cells. We discover that consensus m6A motifs are enriched in circRNAs and a single m6A site is suf- ficient 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.