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论文题目: Extensive translation of circular RNAs driven by N-6-methyladenosine
英文论文题目: Extensive translation of circular RNAs driven by N-6-methyladenosine
第一作者: Yang, Y; Fan, XJ; Mao, MW; Song, XW; Wu, P; Zhang, Y; Jin, YF; Yang, Y; Chen, LL; Wang, Y; Wong, CCL; Xiao, XS; Wang, ZF
英文第一作者: Yang, Y; Fan, XJ; Mao, MW; Song, XW; Wu, P; Zhang, Y; Jin, YF; Yang, Y; Chen, LL; Wang, Y; Wong, CCL; Xiao, XS; Wang, ZF
联系作者: Wang, ZF (reprint author), 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.
英文联系作者: Wang, ZF (reprint author), 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.
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发表年度: 2017
卷: 27
期: 5
页码: 626-641
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.
英文摘要: 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.
刊物名称: CELL RESEARCH
英文刊物名称: CELL RESEARCH
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 15.606
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论文类别: Article
英文论文类别: Article
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