Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) is a tumor suppressor protein that binds site- and structure-specifically to RNA sequences to regulate mRNA stability, facilitate alternative splicing, and suppress protein translation on several metastasis-associated mRNAs. Here, we show that hnRNP E1 binds polycytosine-rich DNA tracts present throughout the genome, including those at promoters of several oncogenes and telomeres and monitors genome integrity. It binds DNA in a site- and structure-specific manner. hnRNP E1-knockdown cells displayed increased DNA damage signals including γ-H2AX at its binding sites and also showed increased mutations. UV and hydroxyurea treatment of hnRNP E1-knockdown cells exacerbated the basal DNA damage signals with increased cell cycle arrest, activation of checkpoint proteins, and monoubiquitination of proliferating cell nuclear antigen despite no changes in deubiquitinating enzymes. DNA damage caused by genotoxin treatment localized to hnRNP E1 binding sites. Our work suggests that hnRNP E1 facilitates functions of DNA integrity proteins at polycytosine tracts and monitors DNA integrity at these sites.

中文翻译：

---

异质核核糖核蛋白 E1 结合多胞嘧啶 DNA 并监测基因组完整性。

异质核核糖核蛋白 E1 (hnRNP E1) 是一种肿瘤抑制蛋白，可与 RNA 序列特异性结合位点和结构，以调节 mRNA 稳定性、促进选择性剪接和抑制几种转移相关 mRNA 上的蛋白质翻译。在这里，我们显示 hnRNP E1 结合存在于整个基因组中的富含多胞嘧啶的 DNA 束，包括几个癌基因和端粒的启动子，并监测基因组的完整性。它以位点和结构特异性的方式结合 DNA。hnRNP E1 敲低细胞在其结合位点显示出增加的 DNA 损伤信号，包括 γ-H2AX，并且还显示出增加的突变。hnRNP E1 敲低细胞的紫外线和羟基脲处理加剧了基础 DNA 损伤信号，增加了细胞周期停滞、检查点蛋白的激活、尽管去泛素化酶没有变化，但增殖细胞核抗原的单泛素化。基因毒素处理引起的 DNA 损伤定位于 hnRNP E1 结合位点。我们的工作表明，hnRNP E1 促进多胞嘧啶束中 DNA 完整性蛋白的功能，并监测这些位点的 DNA 完整性。