MicroRNAs That Contribute to Coordinating the Immune Response in Drosophila melanogaster.
MicroRNAs That Contribute to Coordinating the Immune Response in Drosophila melanogaster.
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DOI：
10.1534/genetics.116.196584
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发表时间：
2017-09
期刊：
影响因子：
3.3
通讯作者：
Ligoxygakis P
中科院分区：
文献类型：
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作者：
Atilano ML;Glittenberg M;Monteiro A;Copley RR;Ligoxygakis P
Atilano等人提出了一种利用miRNA突变果蝇文库的果蝇感染后存活筛选方法。使用全基因组微阵列…被称为microRNAs （miRNAs）的小非编码rna已成为与宿主防御相关的基因表达的转录后调节因子。在这里，我们利用黑腹果蝇来探索单个或集群的mirna在对抗全身白色念珠菌感染中的作用。从总共72个测试中，我们确定了6个miRNA等位基因突变背景，这些突变背景调节了对感染的生存反应和控制病原体数量的能力。这些突变体也表现出Toll通路靶转录物Drosomycin （dr）和免疫诱导分子1 （IM1）的失调。这些都是Toll信号缺陷的特征，与此一致，我们证明了其中一个miRNA突变体对NF-κΒ同源Dif的依赖性。我们还量化了miRNA表达谱随时间的变化，以响应三种病原体类型，并确定了13种成熟的miRNA形式，受病原体刺激Toll信号的影响。为了补充这一点，我们提供了靠近miRNA基因的潜在NF-κB位点的全基因组图谱。最后，我们证明全身白色念珠菌感染有助于减少支链氨基酸总量，这是由mirna调节的。总的来说，我们的数据揭示了一个新的miRNA复杂性层，它调节着苍蝇对全身真菌感染的反应。
Atilano et al. present a Drosophila post-infection survival screen that takes advantage of a library of miRNA mutant flies. Using genome wide microarray.. Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defenses. Here, we have used Drosophila melanogaster to explore the contribution of individual or clusters of miRNAs in countering systemic Candida albicans infection. From a total of 72 tested, we identify 6 miRNA allelic mutant backgrounds that modulate the survival response to infection and the ability to control pathogen number. These mutants also exhibit dysregulation of the Toll pathway target transcripts Drosomycin (Drs) and Immune-Induced Molecule 1 (IM1). These are characteristics of defects in Toll signaling, and consistent with this, we demonstrate dependency for one of the miRNA mutants on the NF-κΒ homolog Dif. We also quantify changes in the miRNA expression profile over time in response to three pathogen types, and identify 13 mature miRNA forms affected by pathogens that stimulate Toll signaling. To complement this, we provide a genome-wide map of potential NF-κB sites in proximity to miRNA genes. Finally, we demonstrate that systemic C. albicans infection contributes to a reduction in the total amount of branch-chained amino acids, which is miRNA-regulated. Overall, our data reveal a new layer of miRNA complexity regulating the fly response to systemic fungal infection.