N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand
N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand
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DOI：
10.1016/j.molcel.2020.12.038
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发表时间：
2021-02-18
期刊：
影响因子：
16
通讯作者：
Wei, Fan-Yan
中科院分区：
文献类型：
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作者：
Ogawa, Akiko;Nagiri, Chisae;Wei, Fan-Yan
在生命的所有王国中已经鉴定了大约150种转录后RNA修饰。在RNA催化过程中，大多数修饰的核苷对降解具有抗性，并被释放到细胞外空间中。在这项研究中，我们探索了这些细胞外修饰核苷的生理作用，发现N-6-甲基腺苷（m（6）A），广泛认为是RNA中的表观遗传标记，作为人腺苷A3受体的配体，它比未修饰的腺苷具有更大的亲和力。我们使用结构建模来定义m（6）A与人A3受体特异性结合所需的氨基酸。我们还证明，m（6）A是动态释放的细胞毒性刺激和促进I型过敏在体内。我们的研究结果表明，m（6）A作为一种信号分子，能够激活G蛋白偶联受体（GPCR），并触发病理生理反应，RNA修饰的一个以前未报道的属性。
About 150 post-transcriptional RNA modifications have been identified in all kingdoms of life. During RNA catabolism, most modified nucleosides are resistant to degradation and are released into the extracellular space. In this study, we explored the physiological role of these extracellular modified nucleosides and found that N-6-methyladenosine (m(6)A), widely recognized as an epigenetic mark in RNA, acts as a ligand for the human adenosine A3 receptor, for which it has greater affinity than unmodified adenosine. We used structural modeling to define the amino acids required for specific binding of m(6)A to the human A3 receptor. We also demonstrated that m(6)A was dynamically released in response to cytotoxic stimuli and facilitated type I allergy in vivo. Our findings implicate m(6)A as a signaling molecule capable of activating G protein-coupled receptors (GPCRs) and triggering pathophysiological responses, a previously unreported property of RNA modifications.