Diazirine Photocrosslinking Recruits Activated FTO Demethylase Complexes for Specific N6-methyladenosine Recognition
Diazirine Photocrosslinking Recruits Activated FTO Demethylase Complexes for Specific N6-methyladenosine Recognition
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DOI：
10.1021/cb5010096
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发表时间：
2015-06-01
影响因子：
4
通讯作者：
Okamoto, Akimitsu
中科院分区：
文献类型：
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作者：
Jeong, Hyun Seok;Hayashi, Gosuke;Okamoto, Akimitsu
N-6-甲基腺苷（m（6）A）是一种常见的RNA修饰。m（6）A存在于mRNA中，在RNA生物学通路和RNA表观遗传调控中起重要作用。我们应用二氮丙啶光交联技术研究了脂肪质量和肥胖相关（FTO）脱甲基酶介导的m（6）A识别事件。RNA上与m（6）A相邻的高度光反应性的二氮杂环丙烷成功地招募了具有m（6）A偏好的活化FTO复合物。使用二氮丙啶光交联通过FTO识别m（6）A的过程由α-酮戊二酸（alpha-KG）共底物和Peal控制。辅因子，它们参与m（6）A氧化去甲基化。此外，FTO在m（6）A识别过程之前与ssRNA结合。二氮丙啶光交联有助于增加捕获具有特异性m（6）A识别的活化FTO复合物的机会，并为动态FTO氧化去甲基化过程提供了新的见解。
N-6-methyladenosine (m(6)A) is a prevalent modification of RNAs. m(6)A exists in mRNA and plays an important role in RNA biological pathways and in RNA epigenetic regulation, We applied diazirine photocrosslinking to the event of m(6)A recognition mediated by the fat mass and obesity associated (FTO) demethylase. A highly photoreactive diazirine adjacent to m(6)A on the RNA successfully recruited activated FTO complexes with an m(6)A preference. The process of recognition of m(6)A via FTO using diazirine photocrosslinking was controlled by the alpha-ketoglutarate (alpha-KG) cosubstrate and the Peal). cofactor, which are involved in m(6)A oxidative demethylation. In addition, FTO bound to ssRNAs prior to the m(6)A recognition process. Diazirine photocrosslinking contributes to increasing the chances of capturing activated FTO complexes with specific m(6)A recognition and provides new insights into the dynamic FTO oxidative demethylation process.