The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian cell survival after UV irradiation
The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian cell survival after UV irradiation
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DOI：
10.1016/j.cub.2003.11.028
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发表时间：
2003-12-16
期刊：
影响因子：
9.2
通讯作者：
Wolin, SL
中科院分区：
文献类型：
--
作者：
Chen, XG;Smith, JD;Wolin, SL
r60kda自身抗原是一种RNA结合蛋白，是系统性红斑狼疮患者免疫反应的主要靶点。当缺乏Ro的小鼠发展为狼疮样综合征时，Ro可能对预防自身免疫性bb0很重要。然而，Ro的细胞功能一直是谜，它结合了功能未知的小细胞质rna，称为Y rna。通过对非洲爪蟾卵母细胞[2]的实验发现，Ro在5S rRNA质量控制中起作用，Ro同源物在紫外线照射[3]后可提高耐辐射球菌真细菌的存活率。为了测试这两个观察结果对Ro功能的一般重要性，我们研究了Ro在哺乳动物细胞中的作用。我们报道，在小鼠胚胎干（ES）细胞中，Ro结合可变剪接体U2 snrna。小鼠U2 snrna在非洲爪蟾卵母细胞中的表达表明，结合发生在细胞核中，似乎涉及对错误折叠RNA的识别。此外，缺乏Ro的小鼠胚胎干细胞在紫外线照射后存活率下降。在受辐照的细胞中，Ro和Y RNA都聚集在细胞核中。我们认为Ro在小RNA质量控制中起着普遍的作用，这一功能对紫外线照射后的细胞存活很重要。
The Ro 60 kDa autoantigen, an RNA binding protein, is a major target of the immune response in patients with systemic lupus erythematosus. As mice lacking Ro develop a lupus-like syndrome, Ro may be important for preventing autoimmunity [1]. However,the cellular function of Ro, which binds small cytoplasmic RNAs of unknown function called Y RNAs, has been enigmatic. Ro has been proposed to function in 5S rRNA quality control based on experiments in Xenopus laevis oocytes [2], and a Ro ortholog enhances survival of the eubacterium Deinococcus radiodurans after ultraviolet irradiation [3]. To test the general importance of these two observations for Ro function, we investigated the role of Ro in mammalian cells. We report that, in mouse embryonic stem (ES) cells, Ro binds variant spliceosomal U2 snRNAs. Expression of mouse U2 snRNAs in Xenopus oocytes reveals that binding occurs in nuclei and appears to involve recognition of misfolded RNA. Moreover, mouse ES cells lacking Ro exhibit decreased survival after ultraviolet irradiation. In irradiated cells, both Ro and a Y RNA accumulate in nuclei. We propose that Ro plays a general role in small RNA quality control and that this function is important for cell survival after ultraviolet irradiation.