The RNA-Protein Interactome of Differentiated Kidney Tubular Epithelial Cells
The RNA-Protein Interactome of Differentiated Kidney Tubular Epithelial Cells
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DOI：
10.1681/asn.2018090914
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发表时间：
2019-04-01
影响因子：
13.6
通讯作者：
Mueller, Roman-Ulrich
中科院分区：
文献类型：
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作者：
Ignarski, Michael;Rill, Constantin;Mueller, Roman-Ulrich
RNA结合蛋白（RBP）是细胞生物学的基本调节因子，影响RNA分子产生和加工的所有步骤。最近的证据表明，调节RNA稳定性和翻译的RBP的调节可能对蛋白质组产生深远的影响。然而，在临床相关的实验conditions.Methods，我们使用RNA相互作用组捕获，一种用于全球识别的RBPs的方法来表征的全球RNA结合蛋白质组（RBPome）与polyA尾的RNA物种在小鼠纤毛上皮细胞的内髓集合管的调节RBPs还没有被系统地研究。为了研究RBPs在临床相关条件下的调节，我们分析了RBPome.Results缺氧相关的变化，我们确定了>1000 RBPs，以前已经发现使用其他系统。此外，我们发现了一些新的RBP没有确定以前的屏幕使用小鼠或人类细胞，这表明这些蛋白质可能是特定的RBP在分化的肾上皮细胞。我们还发现定量差异RBP结合mRNA与缺氧normoxia.Conclusions这些研究结果表明，通过环境刺激的调节RBP，并提供深入了解缺氧反应信号在肾脏上皮细胞的生物学。从我们的研究结果中获得的肾小管上皮细胞中RBPome和蛋白质组的储存库可以在线免费访问，并且可能有助于更好地理解肾小管上皮细胞中RNA-蛋白质相互作用的作用，包括这些细胞对缺氧的反应。
Background RNA-binding proteins (RBPs) are fundamental regulators of cellular biology that affect all steps in the generation and processing of RNA molecules. Recent evidence suggests that regulation of RBPs that modulate both RNA stability and translation may have a profound effect on the proteome. However, regulation of RBPs in clinically relevant experimental conditions has not been studied systematically.Methods We used RNA interactome capture, a method for the global identification of RBPs to characterize the global RNA-binding proteome (RBPome) associated with polyA-tailed RNA species in murine ciliated epithelial cells of the inner medullary collecting duct. To study regulation of RBPs in a clinically relevant condition, we analyzed hypoxia-associated changes of the RBPome.Results We identified >1000 RBPs that had been previously found using other systems. In addition, we found a number of novel RBPs not identified by previous screens using mouse or human cells, suggesting that these proteins may be specific RBPs in differentiated kidney epithelial cells. We also found quantitative differences in RBP-binding to mRNA that were associated with hypoxia versus normoxia.Conclusions These findings demonstrate the regulation of RBPs through environmental stimuli and provide insight into the biology of hypoxia-response signaling in epithelial cells in the kidney. A repository of the RBPome and proteome in kidney tubular epithelial cells, derived from our findings, is freely accessible online, and may contribute to a better understanding of the role of RNA-protein interactions in kidney tubular epithelial cells, including the response of these cells to hypoxia.