The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features.

The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features.
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人腺苷RNA甲基转移酶和去甲基酶的全面相互作用揭示了不同的功能和调节特征。

DOI:
10.1093/nar/gkab900
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发表时间:
2021-11-08
影响因子:
14.9
通讯作者:
Vaňáčová Š
Vaňáčová Š
中科院分区:
生物学2区
文献类型:
--
作者:
Covelo-Molares H;Obrdlik A;Poštulková I;Dohnálková M;Gregorová P;Ganji R;Potěšil D;Gawriyski L;Varjosalo M;Vaňáčová Š

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N6-甲基腺苷(m6 A)和N6,2′-O-二甲基腺苷(m6 Am)是在mRNA和ncRNA中发现的两种丰富的修饰,其可以调节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、疾病和应激反应有关。迄今为止,已经鉴定出三种甲基转移酶和两种脱甲基酶修饰哺乳动物mRNA中的腺苷。在这里,我们提出了一个全面的分析这些酶的相互作用。PCIF 1蛋白网络主要包括参与RNA聚合酶II合成新生RNA的因子,而ALKBH 5与前mRNA加工和mRNA输出到细胞质的大多数方面密切相关。胃L16存在于由几种其他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复制与修复之间的十字路口。总之,这些酶共享有限的空间相互作用组,指向其调节的特定分子机制。
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.
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