文献类型：期刊文献

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

作者：Yang, Yun[1,2,3,4,5];Fan, Xiaojuan[2];Mao, Miaowei[5,6];Song, Xiaowei[1,2,5];Wu, Ping[7,8];Zhang, Yang[9];Jin, Yongfeng[1];Yang, Yi[6];Chen, Ling-Ling[9];Wang, Yang[10];Wong, Catherine C. L.[7,8];Xiao, Xinshu[3,4];Wang, Zefeng[2,5]

机构：[1]Zhejiang Univ, Coll Life Sci, Inst Biochem, Hangzhou 310058, Zhejiang, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Ctr Excellence Mol Cell Sci,CAS Key Lab Compu, Shanghai 200031, Peoples R China;[3]UCLA, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA;[4]Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA;[5]Univ North Carolina Chapel Hill, Dept Pharmacol, Chapel Hill, NC 27599 USA;[6]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Synthet Biol & Biotechnol Lab, Shanghai, Peoples R China;[7]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci, Shanghai 200031, Peoples R China;[8]Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai 201204, Peoples R China;[9]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China;[10]Dalian Med Univ, Inst Canc Stem Cell, Dalian 116044, Liaoning, Peoples R China

年份：2017

卷号：27

期号：5

起止页码：626

外文期刊名：CELL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000400443300007)】；

基金：We want to thank Dr Sonenberg for generous gift of eIF4G2 expression vectors, ENCODE Consortium and Dr Gene Yeo's lab for generating CLIP-seq data sets of eIF4G1, eIF4G2 and eIF3A, and Dr Bill Marzluff for help in polysome fractionation. We thank Shuaixin Gao from the Mass Spectrometry Facility of National Center for Protein Science Shanghai for assistance with MS data collection, database search and quantitation analysis. We thank Dr Xiaoling Li for critical reading of the manuscript. The work is supported by National Natural Science Foundation of China (31570823 to ZW, 31300655 to YY, and 91540110 to YW). The work is also supported by International Postdoctoral Exchange Fellowship to YY, and NIH grant R01HG006264 to XX. MM is supported by a Chinese Scholarship Council Scholarship (201406740040).

语种：英文

外文关键词：N-6-methyladenosine; circular RNA; cap-independent translation; 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-6-methyladenosine (m(6)A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m(6)A motifs are enriched in circRNAs and a single m(6)A site is sufficient to drive translation initiation. This m(6)A-driven translation requires initiation factor eIF4G2 and m(6)A 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 m(6)A-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.