Extensive translation of circular RNAs driven by N super(6)-methyladenosine

Extensive translation of circular RNAs driven by N super(6)-methyladenosine

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 super(6)-methyladenosine (m super(6)A), the most abundant base modification of RNA, promotes efficien...

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Veröffentlicht in:Cell research 2017-05, Vol.27 (5), p.626-641
Hauptverfasser: Yang, Yun, Fan, Xiaojuan, Mao, Miaowei, Song, Xiaowei, Wu, Ping, Zhang, Yang, Jin, Yongfeng, Yang, Yi, Chen, Ling-Ling, Wang, Yang, Wong, Catherine CL, Xiao, Xinshu, Wang, Zefeng
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container_end_page 641
container_issue 5
container_start_page 626
container_title Cell research
container_volume 27
creator Yang, Yun
Fan, Xiaojuan
Mao, Miaowei
Song, Xiaowei
Wu, Ping
Zhang, Yang
Jin, Yongfeng
Yang, Yi
Chen, Ling-Ling
Wang, Yang
Wong, Catherine CL
Xiao, Xinshu
Wang, Zefeng
description 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 super(6)-methyladenosine (m super(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 super(6)A motifs are enriched in circRNAs and a single m super(6)A site is sufficient to drive translation initiation. This m super(6)A-driven translation requires initiation factor eIF4G2 and m super(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 super(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.
doi_str_mv 10.1038/cr.2017.31
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title Extensive translation of circular RNAs driven by N super(6)-methyladenosine
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