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Cap-specific, terminal N6-methylation by a mammalian m6Am methyltransferase

Feb. 15,2019

Dr. Chengqi Yi publised a paper on Cell Research.


Dynamic and reversible N6-methyladenosine (m6A) RNA methylation has been found to greatly impact gene expression, leading to the field of epitranscriptomics. 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 1975; several years later the methyltransferase was partially purified and was proposed to be a species whose molecular weight is ~65 KD. 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 sub-cellular localizations. By changing FTO levels, m6Am at mRNA cap was also suggested to impair DCP2-mediated mRNA decapping. However, the methyltransferase of m6Am is not unambiguously identified, significantly hindering the functional and mechanistic study of m6Am.


Original link: https://www.nature.com/articles/s41422-018-0117-4