miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster
miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster
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miR-958 通过直接靶向黑腹果蝇中的 Toll 和 Dif 抑制 Toll 信号传导和 Drosomycin 表达
DOI：
10.1152/ajpcell.00251.2016
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发表时间：
2017-02-01
影响因子：
5.5
通讯作者：
Ma, Fei
中科院分区：
文献类型：
--
作者：
Li, Shengjie;Li, Yao;Ma, Fei
黑腹果蝇（Drosophila melanogaster）被广泛用作研究先天免疫和先天免疫相关信号通路的模型系统，包括Toll信号通路。尽管这一途径已经得到了很好的研究，但microrna （mirna）对Toll信号通路关键组分的转录后调控的确切机制仍然不清楚。在这项研究中，我们使用了一种结合Gal80(ts)-Gal4驱动系统的芯片策略来鉴定microRNA-958 （miR-958）是果蝇中调节miRNA的一个候选Toll通路。我们报道，miR-958的过表达显著降低了Drosomycin的表达，Drosomycin是一种参与Toll信号传导和先天免疫反应的关键抗菌肽。我们在体外和体内进一步证明，miR-958靶向Toll和Dif基因（Toll信号通路的关键成分）负向调节Drosomycin的表达。此外，miR-958海绵挽救了Toll和Dif的表达，导致Drosomycin的表达增加。这些结果不仅揭示了miR-958的新功能和调节模式，而且为Toll信号在先天免疫调节中的潜在分子机制提供了新的见解。
Drosophila melanogaster is widely used as a model system to study innate immunity and signaling pathways related to innate immunity, including the Toll signaling pathway. Although this pathway is well studied, the precise mechanisms of posttranscriptional regulation of key components of the Toll signaling pathway by microRNAs (miRNAs) remain obscure. In this study, we used an in silico strategy in combination with the Gal80(ts)-Gal4 driver system to identify microRNA-958 (miR-958) as a candidate Toll pathway regulating miRNA in Drosophila. We report that overexpression of miR-958 significantly reduces the expression of Drosomycin, a key antimicrobial peptide involved in Toll signaling and the innate immune response. We further demonstrate in vitro and in vivo that miR-958 targets the Toll and Dif genes, key components of the Toll signaling pathway, to negatively regulate Drosomycin expression. In addition, a miR-958 sponge rescued the expression of Toll and Dif, resulting in increased expression of Drosomycin. These results, not only revealed a novel function and modulation pattern of miR-958, but also provided a new insight into the underlying molecular mechanisms of Toll signaling in regulation of innate immunity.