Activation of Hypoxia-Inducible Factor Signaling Modulates the RNA Protein Interactome in Caenorhabditis elegans
Activation of Hypoxia-Inducible Factor Signaling Modulates the RNA Protein Interactome in Caenorhabditis elegans
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DOI：
10.1016/j.isci.2019.11.039
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发表时间：
2019-12-20
期刊：
影响因子：
5.8
通讯作者：
Fabretti, Francesca
中科院分区：
文献类型：
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作者：
Esmaillie, Reza;Ignarski, Michael;Fabretti, Francesca
细胞对缺氧的反应对生物体的生存至关重要，而缺氧诱导因子（HIF）是这一反应的关键介质。hif信号是许多人类疾病的核心，并介导线虫的寿命。尽管对rna结合蛋白（rbp）的了解迅速增加，但对它们在缺氧诱导的细胞适应中的作用知之甚少。我们在野生型秀丽隐杆线虫和vhl-1功能丧失突变体中使用RNA相互作用组捕获（RIC）来填补这一空白。这种方法鉴定了1300多种线虫rbp，其中270种可以被认为是新的rbp。有趣的是，vhl-1的缺失可以调节RBPome。这种差异并不是主要用蛋白质丰度来解释的，这表明rna结合的差异。综上所述，我们的研究提供了线虫RBPome和蛋白质组以及它们通过hif信号调节的全局视图。生成的RBP图谱也作为交互式在线数据挖掘工具提供（http://shiny.cecad.uni-koeln.de:3838/celegans_rbpome）。
The cellular response to hypoxia is crucial to organismal survival, and hypoxia-inducible factors (HIF) are the key mediators of this response. HIF-signaling is central to many human diseases and mediates longevity in the nematode. Despite the rapidly increasing knowledge on RNA-binding proteins (RBPs), little is known about their contribution to hypoxia-induced cellular adaptation. We used RNA interactome capture (RIC) in wild-type Caenorhabditis elegans and vhl-1 loss-of-function mutants to fill this gap. This approach identifies more than 1,300 nematode RBPs, 270 of which can be considered novel RBPs. Interestingly, loss of vhl-1 modulates the RBPome. This difference is not primarily explained by protein abundance suggesting differential RNA-binding. Taken together, our study provides a global view on the nematode RBPome and proteome as well as their modulation by HIF-signaling. The resulting RBP atlas is also provided as an interactive online data mining tool (http://shiny.cecad.uni-koeln.de:3838/celegans_rbpome).