Wolin Sandra L, Reinisch Karin M
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, United States.
Autoimmun Rev. 2006 Jul;5(6):367-72. doi: 10.1016/j.autrev.2005.10.004. Epub 2005 Nov 15.
A conserved RNA-binding protein, the Ro 60 kDa (Ro60) autoantigen, is a major target of autoantibodies in patients suffering from the rheumatic diseases Sjogren's syndrome, systemic lupus erythematosus, subacute cutaneous lupus erythematosus and neonatal lupus erythematosus. In both mice and certain bacteria, Ro60 is important for cell survival following ultraviolet irradiation. Although the function of Ro60 was mysterious for many years, recent experiments have demonstrated that this protein binds misfolded noncoding RNAs in vertebrate cells and likely functions in a pathway by which defective RNAs are recognized and targeted for degradation. Recent structural studies have revealed that Ro60 is shaped like a doughnut with an inner hole. Noncoding RNAs called Y RNAs bind on the outer surface of the ring, while the single-stranded ends of misfolded RNAs likely bind within the hole. Comparison of the Ro60 structure with the results of epitope-mapping studies reveals that many of the currently identified epitopes recognized by patient sera overlap regions of Ro60 that function in RNA binding. Moreover, in some patients with anti-Ro60 antibodies, the initial antigenic epitope corresponds to a loop involved in binding single-stranded RNA in the central cavity.
一种保守的RNA结合蛋白，即Ro 60 kDa（Ro60）自身抗原，是患有风湿性疾病干燥综合征、系统性红斑狼疮、亚急性皮肤型红斑狼疮和新生儿红斑狼疮患者体内自身抗体的主要靶标。在小鼠和某些细菌中，Ro60对紫外线照射后的细胞存活都很重要。尽管多年来Ro60的功能一直很神秘，但最近的实验表明，这种蛋白在脊椎动物细胞中与错误折叠的非编码RNA结合，可能在识别缺陷RNA并将其靶向降解的途径中发挥作用。最近的结构研究表明，Ro60的形状像一个有内孔的甜甜圈。称为Y RNA的非编码RNA结合在环的外表面，而错误折叠RNA的单链末端可能结合在孔内。将Ro60结构与表位作图研究结果进行比较发现，目前患者血清识别的许多已鉴定表位与Ro60中参与RNA结合的区域重叠。此外，在一些抗Ro60抗体患者中，最初的抗原表位对应于中央腔中参与结合单链RNA的一个环。
