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

Subject Area Cell Biology
Term since 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 503306912
 
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.
DFG Programme Research Units
 
 

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