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Authors :
Chong, Tang
Yeming, Xie
Tian, Yu
Na, Liu
Zhuqing, Wang
Rebekah J, Woolsey
Yunge, Tang
Xinzong, Zhang
Weibing, Qin
Ying, Zhang
Ge, Song
Weiwei, Zheng
Juan, Wang
Weitian, Chen
Xiongyi, Wei
Zhe, Xie
Rachel, Klukovich
Huili, Zheng
David R, Quilici
Wei, Yan
Source :
Cell Res
Publication Year :
2019

Abstract

The majority of circular RNAs (circRNAs) spliced from coding genes contain open reading frames (ORFs) and thus, have protein coding potential. However, it remains unknown what regulates the biogenesis of these ORF-containing circRNAs, whether they are actually translated into proteins and what functions they play in specific physiological contexts. Here, we report that a large number of circRNAs are synthesized with increasing abundance when late pachytene spermatocytes develop into round and then elongating spermatids during murine spermatogenesis. For a subset of circRNAs, the back splicing appears to occur mostly at m(6)A-enriched sites, which are usually located around the start and stop codons in linear mRNAs. Consequently, approximately a half of these male germ cell circRNAs contain large ORFs with m(6)A-modified start codons in their junctions, features that have been recently shown to be associated with protein-coding potential. Hundreds of peptides encoded by the junction sequences of these circRNAs were detected using liquid chromatography coupled with mass spectrometry, suggesting that these circRNAs can indeed be translated into proteins in both developing (spermatocytes and spermatids) and mature (spermatozoa) male germ cells. The present study discovered not only a novel role of m(6)A in the biogenesis of coding circRNAs, but also a potential mechanism to ensure stable and long-lasting protein production in the absence of linear mRNAs, i.e., through production of circRNAs containing large ORFs and m(6)A-modified start codons in junction sequences.

Details

ISSN :
17487838
Volume :
30
Issue :
3
Database :
OpenAIRE
Journal :
Cell research
Accession number :
edsair.pmid..........5b1e5aad7d81853630aadd20ef79279e