m6A甲基化酶ZCCHC4结合EIF3复合物调节翻译的机制研究

RNA修饰有着多种多样的生物学功能，参与RNA修饰的酶除酶活之外，还可以通过与细胞内的其它蛋白相互作用，有着酶活之外的功能。我们前期发现并首次报道了一个新的RNA甲基化酶ZCCHC4，它能特异催化28S rRNA的m6A修饰，我们最新研究发现它还与翻译起始复合物EIF3相互作用，敲低或者敲除实验表明它能调节靶mRNA c-MYC的蛋白水平，报告基因分析显示该调节需要EIF3等翻译起始因子作用，具体的机制还有待我们进一步研究，大规模的RNA干扰筛选显示ZCCHC4能抑制Kras突变的肿瘤形成，以及HBV的复制，我们的研究将进一步揭示ZCCHC4翻译调节的机制与肿瘤形成以及HBV复制的关系，针对ZCCHC4的研究将为我们在抑制剂以及药物的设计上提供指导。

RNA modification has a variety of biological functions. In addition to enzymatic activity, RNA methyltransferase involved in RNA modification can also function outside the enzyme by interacting with other proteins in the cell. We have previously discovered and reported a new RNA methylase ZCCHC4, which specifically catalyzes the m6A modification of 28S rRNA. Our latest study found that it also interacts with the translation initiation complex EIF3, knockdown or knockout experiments show It regulates the protein level of the target mRNA c-MYC. Reporter assay analysis indicates that this regulation requires the translation initiation factor such as EIF3 complex. The specific mechanism remains to be further studied. Large-scale RNA interference screening shows that ZCCHC4 can inhibit the tumorigenicity of K-ras-transformed cells, as well as replication of HBV, our study will further reveal the mechanism by which ZCCHC4 regulates translation and the relationship between of tumor formation and HBV replication. The study of ZCCHC4 will provide guidance for the design of inhibitors and medicine.