RNA表观遗传修饰：N＾6-甲基腺嘌呤

RNA epigenetic modification: N^6-methyladenosine

N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA(Messenger RNA,m RNA)上含量最多的化学修饰之一。类似于DNA和组蛋白化学修饰,m6A修饰也同样是动态可逆的,可在时间和空间上被甲基转移酶和去甲基酶调控。哺乳动物体内m6A甲基转移酶复合物中有一部分成分已被解析,主要有METTL3(Methyltransferase-like protein 3)、METTL14(Methyltransferase-like protein 14)和WTAP(Wilms tumor 1-associating protein)。m6A去甲基酶肥胖蛋白FTO(Fat mass and obesity associated protein)和ALKBH5(Alk B homolog 5)依赖α-酮戊二酸(α-Ketoglutaric acid,α-KG)和Fe(Ⅱ)对m6A进行氧化去甲基化反应。m6A在生物体内由m6A结合蛋白识别,并介导其行使功能。目前发现的m6A结合蛋白有YTH结构域蛋白YTHDF1(YTH domain-containing family protein 1)、YTHDF2(YTH domain-containing family protein 2)、YTHDC1(YTH domain-containing protein1)和核内HNRNPA2B1(Heterogeneous nuclear ribonucleoproteins A2B1)。本文综述了m6A的分布和相关蛋白介导的m6A功能研究,以期全面理解m6A这一RNA表观遗传新修饰在生命进程中的重要调控作用。

N^6-methyladenosine（m^6A） is one of the most prevalent internal modifications in eukaryotic messenger RNA. The dynamic and reversible modification is installed by methyltransferase complex charactered three subunits： METTL3（Methyltransferase-like protein 3）, METTL14（Methyltransferase-like protein 14） and WTAP（Wilms tumor 1-associating protein）, and erased by two independent demethylases, FTO（Fat mass and obesity associated protein） and ALKBH5（Alk B homolog 5）, in an α-ketoglutarate（α-KG）- and Fe（II）-dependent manner. m^6 A plays funtions in controlling RNA metabolism through the recognition by m^6 A reader proteins, the YTH domain family proteins and HNRNPA2B1（Heterogeneous nuclear ribonucleoproteins A2B1）. In this review, we summarized distributive features and vital roles of m^6 A and its associated proteins in RNA metabolisms and biological significance, which will help us better understand this new exciting emerging epitranscriptome research field.