Cap-specific, terminal N6-methylation by a mammalian m6Am methyltransferase
Dear Editor,Dynamic and reversibleN6-methyladenosine (m6A) RNA methylation has been found to greatly impact gene expression,leading to the field of epitranscriptomics.1 Unlike m6A that is an internal modification,a terminal modification at mRNA cap in higher eukaryotes exists,termed as N6,2”-O-dimethyladenosine (m6Am) (Fig.1a).The first and sometimes the second nucleotide after the N7-methylguanosine (m7G) cap can be methylated at the 2”-hydroxyl group;and when the first nucleotide is 2”-O-methyladenosine (Am),it can be further methylated at the N6 position to become m6Am.m6Am was first identified in animal cells and virus mRNA in 19752;several years later the methyltransferase was partially purified and was proposed to be a species whose molecular weight is ～65 KD.3 Only very recently,m6Am was found to be reversible as well:the first m6A demethylase FTO also catalyzed the demethylation of m6Am,depending on its subcellular Iocalizations.4,5 By changing FTO levels,m6Am at mRNA cap was also suggested to impair DCP2-mediated mRNA decapping.4 However,the methyltransferase of m6Am is not unambiguously identified,significantly hindering the functional and mechanistic study of m6Am.
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The authors would like to thank Shengxian Gao and Shaokai Ning for helping with HEK293 suspension cell culture, Menghao Liu and Yuxiang Liu for technological advice of protein purification, Xushen Xiong for advice on bioinformatics analysis,Xiaoyu Li for discussions, Dong Liu for assistance with pronos. 91 7401 12 and 21 82570 to C.Y.;the National Basic Research Foundation of Chinano. 2016YFC0900301;the Joint Laboratory of International Scientific and Technological Cooperation
2019-03-08（万方平台首次上网日期，不代表论文的发表时间）
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80-82
