Yang Chuanbin, Huang Shaofei, Wang Xuanbin, Gu Yong
School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Crit Rev Eukaryot Gene Expr. 2015;25(1):77-89. doi: 10.1615/critreveukaryotgeneexpr.2015013022.
Posttranscriptional gene regulation is a rapid and effective way to mediate the expression of inflammatory genes. CCCH-type zinc finger proteins are nucleotide-binding molecules involved in RNA metabolism pathways such as RNA splicing, polyadenylation, and messenger RNA (mRNA) decay. Among these proteins, tristetraproline, Roquins, and Regnase-1/monocyte chemotactic protein-1-induced protein-1 have been recently reported to be responsible for mRNA instability. They bind to mRNAs harboring unique motifs and induce mRNA decay. In this review we summarize current progress regarding the specific characteristics of sequences and structures in the 3' untranslated regions of mRNAs that are recognized by tristetraproline, Roquins, and Regnase-1. The target mRNAs to be destabilized by those CCCH-type zinc finger proteins also are included. Notably, most target mRNAs encode cytokines and other inflammatory mediators, suggesting the immune regulation role of CCCH zinc finger proteins. Mice carrying a genetic null allele or modification of these genes display severe symptoms of autoimmune diseases. Taken together, data show that CCCH-type zinc finger proteins play a crucial role in regulating immune response by targeting multiple mRNAs, and including decay. Further understanding the functions of these proteins may provide new therapeutic targets for immune-related disorders in the future.
转录后基因调控是介导炎症基因表达的一种快速有效的方式。CCCH型锌指蛋白是参与RNA代谢途径（如RNA剪接、多聚腺苷酸化和信使核糖核酸（mRNA）降解）的核苷酸结合分子。在这些蛋白质中，三聚四脯氨酸、罗氏蛋白和Regnase-1/单核细胞趋化蛋白-1诱导蛋白-1最近被报道与mRNA的不稳定性有关。它们与含有独特基序的mRNA结合并诱导mRNA降解。在这篇综述中，我们总结了目前关于三聚四脯氨酸、罗氏蛋白和Regnase-1所识别的mRNA 3'非翻译区序列和结构的具体特征的研究进展。还包括那些会被这些CCCH型锌指蛋白使其不稳定的靶mRNA。值得注意的是，大多数靶mRNA编码细胞因子和其他炎症介质，这表明CCCH锌指蛋白具有免疫调节作用。携带这些基因的无效等位基因或发生基因修饰的小鼠表现出自身免疫性疾病的严重症状。综上所述，数据表明CCCH型锌指蛋白通过靶向多种mRNA（包括使其降解）在调节免疫反应中起关键作用。进一步了解这些蛋白质的功能可能为未来免疫相关疾病提供新的治疗靶点。
