Helmholtz Zentrum München, Institute of Molecular Immunology, Munich, Germany.
Immunol Rev. 2013 May;253(1):273-89. doi: 10.1111/imr.12056.
Post-transcriptional gene regulation by RNA-binding proteins is a fast and effective way to adapt gene expression and change cellular responses. These trans-acting factors have been involved in a number of cell fate decisions, and their mutation is often associated with the development of disease. The RNA-binding protein Roquin-1 has been found to be crucial in the maintenance of peripheral tolerance and the prevention of autoimmune disease. This review describes the molecular role of Roquin family proteins in the control of follicular T-helper cell differentiation. Here, we discuss the redundant regulation of Icos and Ox40 costimulatory receptor mRNAs by Roquin-1 and Roquin-2 proteins. A major focus is placed on the distinct activity of Roquin-1 or Roquin-2 proteins in the mouse models of conditional gene targeting. These recent data are then integrated into an interpretation of altered Roquin protein function in the sanroque mouse that expresses the Roquin-1 protein with just one amino acid substitution and, different from the Roquin-1-deficient mouse, develops lupus-like autoimmune disease.
RNA 结合蛋白的转录后基因调控是一种快速有效的适应基因表达和改变细胞反应的方式。这些反式作用因子参与了许多细胞命运决定，其突变通常与疾病的发展有关。RNA 结合蛋白 Roquin-1 被发现对维持外周耐受和预防自身免疫性疾病至关重要。本文描述了 Roquin 家族蛋白在控制滤泡辅助性 T 细胞分化中的分子作用。在这里，我们讨论了 Roquin-1 和 Roquin-2 蛋白对 Icos 和 Ox40 共刺激受体 mRNA 的冗余调控。重点是 Roquin-1 或 Roquin-2 蛋白在条件性基因靶向小鼠模型中的独特活性。然后，将这些最新数据整合到对 sanroque 小鼠中改变的 Roquin 蛋白功能的解释中，该小鼠表达的 Roquin-1 蛋白只有一个氨基酸取代，与 Roquin-1 缺陷型小鼠不同，会发展出狼疮样自身免疫性疾病。
