A Light-Controllable Chemical Modulation of m6A RNA Methylation
A Light-Controllable Chemical Modulation of m6A RNA Methylation
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m6A RNA 甲基化的光控化学调节
DOI：
10.1002/anie.202103854
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发表时间：
2021-07-09
影响因子：
16.6
通讯作者：
Cheng, Liang
中科院分区：
文献类型：
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作者：
Lan, Ling;Sun, Ying-Jie;Cheng, Liang
具有光可去除保护基团的生物活性小分子提供了相应生物效应的空间和时间控制。我们介绍了第一个光激活小分子甲基转移酶激动剂的设计、合成、计算和实验评估。通过用光可去除的邻硝基苯甲基部分阻断 MPCH 上的功能性 N-H 基团，我们开发了一种有前途的光笼化合物，该化合物完全隐藏了其生物活性。用这种笼状分子处理的细胞在几分钟内短时间紫外光照射会导致转录组 RNA 中 m(6)A 修饰的显着超甲基化，这意味着母体活性化合物的快速释放。这项研究首次验证了RNA表观遗传学研究领域中光激活有机小分子的概念，它代表了时空和细胞调制方法中的一种新工具。
Bioactive small molecules with photo-removable protecting groups have provided spatial and temporal control of corresponding biological effects. We present the design, synthesis, computational and experimental evaluation of the first photo-activatable small-molecule methyltransferase agonist. By blocking the functional N-H group on MPCH with a photo-removable ortho-nitrobenzyl moiety, we have developed a promising photo-caged compound that had completely concealed its biological activity. Short UV light exposure of cells treated with that caged molecule in a few minutes resulted in a considerable hypermethylation of m(6)A modification in transcriptome RNAs, implicating a rapid release of the parent active compound. This study validates for the first time the photo-activatable small organic molecular concept in the field of RNA epigenetic research, which represents a novel tool in spatiotemporal and cellular modulation approaches.