Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213003, China.
Heart and Lung Disease Laboratory, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213003, China.
Biomolecules. 2022 Sep 2;12(9):1224. doi: 10.3390/biom12091224.
Wilms' tumor 1-associating protein (WTAP) is required for N-methyladenosine (mA) RNA methylation modifications, which regulate biological processes such as RNA splicing, cell proliferation, cell cycle, and embryonic development. mA is the predominant form of mRNA modification in eukaryotes. WTAP exerts mA modification by binding to methyltransferase-like 3 (METTL3) in the nucleus to form the METTL3-methyltransferase-like 14 (METTL14)-WTAP (MMW) complex, a core component of the methyltransferase complex (MTC), and localizing to the nuclear patches. Studies have demonstrated that WTAP plays a critical role in various cancers, both dependent and independent of its role in mA modification of methyltransferases. Here, we describe the recent findings on the structural features of WTAP, the mechanisms by which WTAP regulates the biological functions, and the molecular mechanisms of its functions in various cancers. By summarizing the latest WTAP research, we expect to provide new directions and insights for oncology research and discover new targets for cancer treatment.
Wilms 瘤 1 相关蛋白 (WTAP) 是 N-甲基腺苷 (mA) RNA 甲基化修饰所必需的，该修饰调节 RNA 剪接、细胞增殖、细胞周期和胚胎发育等生物学过程。mA 是真核生物中 mRNA 修饰的主要形式。WTAP 通过与核内的甲基转移酶样 3 (METTL3) 结合，形成 METTL3-甲基转移酶样 14 (METTL14)-WTAP (MMW) 复合物，作为甲基转移酶复合物 (MTC) 的核心组成部分，定位于核斑，从而发挥 mA 修饰作用。研究表明，WTAP 在各种癌症中发挥着关键作用，这与其在甲基转移酶 mA 修饰中的作用既有关联，也有独立性。本文描述了 WTAP 的结构特征、调节生物学功能的机制以及其在各种癌症中的功能的分子机制等方面的最新发现。通过总结最新的 WTAP 研究，我们希望为肿瘤学研究提供新的方向和见解，并发现癌症治疗的新靶点。
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