Dynamic regulation of ciliary RNA-binding proteins in kidney epithelial cells

多囊肾病（pkd）是由纤毛蛋白编码基因突变引起的，是纤毛病的重要表现。有趣的是，大多数致病性突变并不完全取消纤毛发生，而是干扰动态纤毛功能，如纤毛蛋白运输和信号传导或纤毛组装-拆卸循环。最近，我们发现RNA结合蛋白（rbp）和RNA是初级纤毛的新成分，它们在诱导纤毛拆卸时受到动态调节和富集。在我们的初步工作中，我们已经确认了RNA编辑酶Adar1和细胞周期相关蛋白1 （Caprin-1）的纤毛定位。此外，我们在初级纤毛中检测到了双链RNA。rbp和RNA在纤毛动力学中的作用尚不清楚。当前项目的总体目标是了解rbp和RNA在纤毛和细胞质之间的动态穿梭，以及rbp和RNA在纤毛组装和拆卸的周期性循环中的作用。这将在其对复杂组织，肾脏组织的影响的背景下进行检查。特别是，我们将(1)描述单个rbp和RNA在纤毛特异性定位的动力学特征，(2)研究纤毛rbp和RNA如何调节纤毛的组装/拆卸和信号传导，以及(3)旨在了解纤毛rbp的丢失对肾脏组织的影响。

Polycystic kidney diseases (PKDs) are caused by mutations in genes encoding for ciliary proteins and constitute a significant manifestation of ciliopathies. Interestingly, most pathogenic mutations do not entirely abrogate ciliogenesis but rather interfere with dynamic ciliary functions such as ciliary protein trafficking and signaling or the ciliary assembly-disassembly cycle. Recently, we identified RNA-binding proteins (RBPs) and RNA as novel components of primary cilia, that are dynamically regulated and enriched upon induction of ciliary disassembly. In our preliminary work, we could already confirm the ciliary localization for the RNA editing enzyme Adar1 and the Cell cycle associated protein 1 (Caprin-1). Besides, we detected double-stranded RNA in primary cilia. The role of RBPs and RNA in cilia dynamics is not understood. The overarching aim of the project at-hand is to understand the dynamic shuttling of RBPs and RNA between the cilium and the cytosol, and the role of RBPs and RNA within the periodic cycle of ciliary assembly and disassembly. This will be examined in the context of its impact on the organization of a complex tissue, the kidney. In particular, we will (1) characterize the dynamics of cilia-specific localization of individual RBPs and RNA, (2) investigate how ciliary RBPs and RNA modulate ciliary assembly/disassembly and signaling, and (3) aim to understand the impact of loss of ciliary RBPs on renal tissue organization.