N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation.

中文翻译：

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人腺苷 RNA 甲基转移酶和去甲基化酶的综合相互作用组揭示了不同的功能和调控特征

N6-甲基腺苷 (m6A) 和 N6,2'-O-二甲基腺苷 (m6Am) 是在 mRNA 和 ncRNA 中发现的两种丰富的修饰，可以调节 RNA 生物学的多个方面。它们主要通过调节与特定 RNA 结合蛋白的相互作用来发挥作用。这两种修饰都与发育、疾病和压力反应有关。迄今为止，已鉴定出三种甲基转移酶和两种去甲基化酶可修饰哺乳动物 mRNA 中的腺苷。在这里，我们对这些酶的相互作用组进行了全面分析。PCIF1 蛋白网络主要包含参与 RNA 聚合酶 II 合成新生 RNA 的因子，而 ALKBH5 与前 mRNA 加工和 mRNA 输出到细胞质的大部分方面密切相关。METTL16 位于由其他几种 RNA 修饰剂和加工因子共同居住的亚细胞区室中。FTO 相互作用组将这种去甲基化酶定位在 RNA 转录、RNA 加工和 DNA 复制和修复之间的十字路口。总而言之，这些酶共享有限的空间相互作用组，指向它们调控的特定分子机制。