Dai Xin-Yuan, Shi Liang, Li Zhi, Yang Hai-Yan, Wei Ji-Fu, Ding Qiang
Jiangsu Breast Disease Center, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China.
Research Division of Clinical Pharmacology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China.
Front Oncol. 2021 Apr 13;11:635329. doi: 10.3389/fonc.2021.635329. eCollection 2021.
Among the over 150 RNA modifications, N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNAs, not only in messenger RNAs, but also in microRNAs and long non-coding RNAs. It is a dynamic and reversible process in mammalian cells, which is installed by "writers," consisting of METTL3, METTL14, WTAP, RBM15/15B, and KIAA1429 and removed by "erasers," including FTO and ALKBH5. Moreover, m6A modification is recognized by "readers," which play the key role in executing m6A functions. IYT521-B homology (YTH) family proteins are the first identified m6A reader proteins. They were reported to participate in cancer tumorigenesis and development through regulating the metabolism of targeted RNAs, including RNA splicing, RNA export, translation, and degradation. There are many reviews about function of m6A and its role in various diseases. However, reviews only focusing on m6A readers, especially YTH family proteins are few. In this review, we systematically summarize the recent advances in structure and biological function of YTH family proteins, and their roles in human cancer and potential application in cancer therapy.
在150多种RNA修饰中，N6-甲基腺苷（m6A）是真核生物RNA中最丰富的内部修饰，不仅存在于信使RNA中，也存在于微小RNA和长链非编码RNA中。在哺乳动物细胞中，这是一个动态且可逆的过程，由包括METTL3、METTL14、WTAP、RBM15/15B和KIAA1429在内的“书写器”进行修饰，并由包括FTO和ALKBH5在内的“擦除器”去除。此外，m6A修饰由“读取器”识别，这些“读取器”在执行m6A功能中起关键作用。IYT521-B同源性（YTH）家族蛋白是最早被鉴定出的m6A读取蛋白。据报道，它们通过调节靶向RNA的代谢参与癌症的发生和发展，包括RNA剪接、RNA输出、翻译和降解。关于m6A的功能及其在各种疾病中的作用有很多综述。然而，仅关注m6A读取器，尤其是YTH家族蛋白的综述很少。在本综述中，我们系统地总结了YTH家族蛋白的结构和生物学功能的最新进展，以及它们在人类癌症中的作用和在癌症治疗中的潜在应用。
