RNA molecules harbor diverse modifications that play important regulatory roles in a variety of biological processes. Over 150 modifications have been identified in RNA molecules. N6-methyladenosine (m6A) and 1-methyladenosine (m1A) are prevalent modifications occurring in various RNA species of mammals. Apart from the single methylation of adenosine (m6A and m1A), dual methylation modification occurring in the nucleobase of adenosine, such as N6,N6-dimethyladenosine (m6,6A), also has been reported to be present in RNA of mammals. Whether there are other forms of dual methylation modification occurring in the nucleobase of adenosine other than m6,6A remains elusive. Here, we reported the existence of a novel adenosine dual methylation modification, i.e. 1,N6-dimethyladenosine (m1,6A), in tRNAs of living organisms. We confirmed that m1,6A is located at position 58 of tRNAs and is prevalent in mammalian cells and tissues. The measured level of m1,6A ranged from 0.0049% to 0.047% in tRNAs. Furthermore, we demonstrated that TRMT6/61A could catalyze the formation of m1,6A in tRNAs and m1,6A could be demethylated by ALKBH3. Collectively, the discovery of m1,6A expands the diversity of RNA modifications and may elicit a new tRNA modification-mediated gene regulation pathway.

RNA 分子具有多種修飾，這些修飾在各種生物過程中發(fā)揮著重要的調節(jié)作用。已在 RNA 分子中鑒定出超過 150 種修飾。N6-甲基腺苷 ( m6 A) 和 1-甲基腺苷 (m1A) 是哺乳動物的各種 RNA 物種中普遍存在的修飾。除了腺苷的單甲基化（m6A 和 m1A）外，據(jù)報道，在腺苷的核堿基中發(fā)生的雙重甲基化修飾，例如 N6, N 6-二甲基腺苷 (m6,6A)，也存在于哺乳動物的 RNA 中。除了 m6,6A 之外，腺苷的核堿基中是否存在其他形式的雙重甲基化修飾仍然難以捉摸。

近日，武漢大學袁必鋒團隊在Nucleic Acids Research （IF=19）在線發(fā)表題為“Formation and removal of 1, N 6-dimethyladenosine in mammalian transfer RNA ”的研究論文，該研究報告了在活生物體的 tRNA 中存在一種新的腺苷雙甲基化修飾，即 1,N6-二甲基腺苷 (m1,6A)。該研究采用了我司生產(chǎn)的 鏈霉親和素磁珠PuriMag G-strep釣取RNA。

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