生物
N6-甲基腺苷
翻译(生物学)
转录组
核糖核酸
多形体
核糖体分析
计算生物学
RNA剪接
脱甲基酶
真核翻译
平动调节
环状RNA
信使核糖核酸
细胞生物学
核糖体
基因
遗传学
甲基转移酶
基因表达
组蛋白
甲基化
作者
Yun Yang,Xiaojuan Fan,Miaowei Mao,Xuehang Song,Ping Wu,Yang Zhang,Yongfeng Jin,Yi Yang,Ling Ling Chen,Yang Wang,Catherine C. L. Wong,Xinshu Xiao,Zefeng Wang
出处
期刊:Cell Research
[Springer Nature]
日期:2017-03-10
卷期号:27 (5): 626-641
被引量:1341
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.
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