Mechanisms and strategies for determining m6A RNA modification sites by natural and engineered m6A effector proteins

Mechanisms and strategies for determining m6A RNA modification sites by natural and engineered m6A effector proteins
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通过天然和工程化 m6A 效应蛋白确定 m6A RNA 修饰位点的机制和策略

DOI:
10.1002/asia.202200367
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发表时间:
2022
期刊:
Chem. Asian J.
影响因子:
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通讯作者:
M. Imanishi
M. Imanishi
中科院分区:
--
文献类型:
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作者:
Sakaguchi Kana;Tamiaki Hitoshi;吉田将人,松下朝哉,木越英夫;奥村正樹;M. Imanishi

文献摘要

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N6-甲基腺苷 (m6A) 是 5'-RRACH-3' 共有序列中最常见的内部 RNA 修饰。甲基标记由写入蛋白(METTL3/METTL14 甲基转移酶复合物)添加,并由擦除蛋白(m6A 去甲基酶;FTO 和 ALKBH5)去除。 m6A 阅读器蛋白对甲基标记的识别会导致 RNA 代谢发生变化。尽管这些信息对于理解 m6A 的调节机制和生理作用非常重要,但写入蛋白和擦除蛋白如何确定其目标尚不清楚。然而,正在开发针对特定位点甲基化状态进行靶向操作的方法。在这篇综述中,我总结了 m6A 调节蛋白靶标识别机制的最新发现,以及靶向 m6A 修饰的最新方法。
N6‐Methyladenosine (m6A) is the most common internal RNA modification in the consensus sequence of 5′‐RRACH‐3′. The methyl mark is added by writer proteins (METTL3/METTL14 metyltransferase complex) and removed by eraser proteins (m6A demethylases; FTO and ALKBH5). Recognition of this methyl mark by m6A reader proteins leads to changes in RNA metabolism. How the writer and eraser proteins determine their targets is not well‐understood, despite the importance of this information in understanding the regulatory mechanisms and physiological roles of m6A. However, approaches for targeted manipulation of the methylation state at specific sites are being developed. In this review, I summarize the recent findings on the mechanisms of target identification of m6A regulatory proteins, as well as recent approaches for targeted m6A modifications.