m^6A-dependent biogenesis of circular RNAs in male germ cells  

作　　者：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 

机构地区：[1]Department of Physiology and Cell Biology,University of Nevada,Reno School of Medicine,Reno,NV 89557,USA [2]BGI Co.Ltd.,Shenzhen 518083,China [3]Nevada Proteomics Center,University of Nevada,Reno,Reno,NV 89557,USA [4]Key Laboratory of Male Reproduction and Genetics,National Health and Family Planning Commission,No.17 Meidong Road,Yuexiu District,Guangzhou 510600,China [5]Family Planning Research Institute of Guangdong Province,No.17 Meidong Road,Yuexiu District,Guangzhou 510600,China [6]Department of Cell Biology and Physiology,University of Copenhagen 13,2100 Copenhagen,Denmark [7]Department of Obstetrics and Gynecology,University of Nevada,Reno,School of Medicine,Reno,NV 89557,USA [8]Department of Biology,University of Nevada,Reno,Reno,NV 89557,USA

出　　处：《Cell Research》2020年第3期211-228,共18页细胞研究（英文版）

基　　金：supported by grants from the NIH(HD071736 and HD085506 to W.Y.);the Templeton Foundation(PID:61174 to W.Y.);RNA-seq was conducted in the Single Cell Genomics Core of the University of Nevada,Reno School of Medicine,which was supported,in part,by the NIH COBRE Grant(P30GM110767 to W.Y.);Bioinformatics and RPAD-seq were,in part,carried out in the BGI Co.Ltd,with the support of a grant from the Science,Technology and Innovation Commission of Shenzhen Municipality(JSGG20170824152728492 to C.T.);supported by grants from the Natural Science Foundation of Guangdong Province(2015A030313884 and 2018A030313528 to Y.T.and W.Q.);the Science and Technology Projects of Guangzhou(201607010137 and 201804010431 to W.Q.and Y.T.);the Family Planning Research Institute of Guangdong Province(S2014001 to Y.T.).

摘　　要：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^6A-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^6A-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^6A 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^6A-modified start codons in junction sequences.

关 键 词：CIRCULAR mostly FRAMES 

分 类 号：Q522[生物学—生物化学]