Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
Nat Commun. 2013;4:2273. doi: 10.1038/ncomms3273.
Deamination of DNA bases can create missense mutations predisposing humans to cancer and also interfere with other basic molecular genetic processes; this deamination generates deoxyinosine from deoxyadenosine. In Escherichia coli, the highly conserved endonuclease V is involved in alternative excision repair that removes deoxyinosine from DNA. However, its exact activities and roles in humans are unknown. Here we characterize the FLJ35220 protein, the human homologue of E. coli endonuclease V, hEndoV as a ribonuclease specific for inosine-containing RNA. hEndoV preferentially binds to RNA and efficiently hydrolyses the second phosphodiester bond located 3' to the inosine in unpaired inosine-containing ssRNA regions in dsRNA. It localizes to the cytoplasm in cells. The ribonuclease activity is promoted by Tudor staphylococcal nuclease and detected on inosine-containing dsRNA created by the action of adenosine deaminases acting on RNA. These results demonstrate that hEndoV controls the fate of inosine-containing RNA in humans.
DNA 碱基的脱氨作用会导致错义突变，使人类易患癌症，还会干扰其他基本的分子遗传过程；这种脱氨作用会将脱氧腺苷转化为脱氧肌苷。在大肠杆菌中，高度保守的内切核酸酶 V 参与替代切除修复，从 DNA 中去除脱氧肌苷。然而，其在人类中的确切活性和作用尚不清楚。在这里，我们将大肠杆菌内切核酸酶 V 的人类同源物 FLJ35220 蛋白 hEndoV 鉴定为一种特异性识别含肌苷 RNA 的核糖核酸酶。hEndoV 优先结合 RNA，并能有效水解 dsRNA 中未配对含肌苷 ssRNA 区域中位于肌苷 3'位的第二个磷酸二酯键。它在细胞中定位于细胞质。核糖核酸酶活性由 Tudor 葡萄球菌核酸酶促进，并在 RNA 作用下的腺苷脱氨酶产生的含肌苷 dsRNA 上检测到。这些结果表明 hEndoV 控制了人类含肌苷 RNA 的命运。
