N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation
N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation
复制标题
N-6-甲基腺苷甲基转移酶 ZCCHC4 介导核糖体 RNA 甲基化
DOI：
10.1038/s41589-018-0184-3
复制
发表时间：
2019-01-01
影响因子：
14.8
通讯作者：
He, Chuan
中科院分区：
文献类型：
--
作者：
Ma, Honghui;Wang, Xiaoyun;He, Chuan
N-6-甲基腺苷（m（6）A）RNA修饰存在于人类的信使RNA（mRNA）、核糖体RNA（rRNA）和剪接体RNA（snRNA）中。虽然mRNA m（6）A修饰已被广泛研究，并显示在许多细胞过程中发挥关键作用，但rRNA的m（6）A甲基转移酶的身份和rRNA m（6）A修饰的功能尚不清楚。在这里，我们报告了一个新的m（6）A甲基转移酶，ZCCHC 4，主要甲基化人类28 S rRNA，也与一个子集的mRNA相互作用。ZCCHC 4基因敲除消除了28 SrRNA中的m6 A4220修饰，减少了整体翻译，抑制了细胞增殖.我们还发现ZCCHC 4蛋白在肝细胞癌肿瘤中过表达，并且ZCCHC 4敲除显著减小了异种移植小鼠模型中的肿瘤大小。我们的研究结果突出了rRNA m（6）A修饰在翻译和肿瘤生物学中的功能意义。
N-6-Methyladenosine (m(6)A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m(6)A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m(6)A methyltransferases for rRNAs and the function of rRNA m(6)A modifications are unknown. Here we report a new m(6)A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m 6 A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m(6)A modification in translation and in tumor biology.