Extensive Translation of Circular RNAs Driven by N-methyladenosine

Overview

Journal Cell Res

Specialty Cell Biology

Date 2017 Mar 11

PMID 28281539

Citations 1004

Authors

Yun Yang

Xiaojuan Fan

Miaowei Mao

Xiaowei Song

Ping Wu

Yang Zhang

Yongfeng Jin

Yi Yang

Ling-Ling Chen

Yang Wang

Catherine Cl Wong

Xinshu Xiao

Zefeng Wang

Affiliations

Soon will be listed here.

Abstract

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 (mA), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus mA motifs are enriched in circRNAs and a single mA site is sufficient to drive translation initiation. This mA-driven translation requires initiation factor eIF4G2 and mA 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 mA-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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