Atilano Magda L, Glittenberg Marcus, Monteiro Annabel, Copley Richard R, Ligoxygakis Petros
Laboratory of Cell Biology, Development and Genetics, Department of Biochemistry, University of Oxford, OX1 3QU, United Kingdom.
Sorbonne Universités, Université Pierre et Marie Curie University Paris 06, Centre Nationnal de la Recherche Scientifique, Laboratoire de Biologie du Développement de Villefranche-sur-mer, 06230, France.
Genetics. 2017 Sep;207(1):163-178. doi: 10.1534/genetics.116.196584. Epub 2017 Jul 13.
Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defenses. Here, we have used to explore the contribution of individual or clusters of miRNAs in countering systemic 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 () and (). 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 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.
被称为微小RNA（miRNA）的小型非编码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[具体方法]来探究单个或成簇的miRNA在对抗全身性真菌感染中的作用。在总共测试的72个[对象]中，我们鉴定出6种miRNA等位基因突变背景，它们可调节对感染的存活反应以及控制病原体数量的能力。这些突变体还表现出Toll途径靶转录本（[具体转录本1]）和（[具体转录本2]）的失调。这些是Toll信号传导缺陷的特征，与此一致的是，我们证明了其中一个miRNA突变体对NF-κΒ同源物Dif的依赖性。我们还量化了miRNA表达谱随时间对三种病原体类型的反应变化，并鉴定出13种受刺激Toll信号传导的病原体影响的成熟miRNA形式。作为补充，我们提供了miRNA基因附近潜在NF-κB位点的全基因组图谱。最后，我们证明全身性真菌感染会导致支链氨基酸总量减少，这是由miRNA调节的。总体而言，我们的数据揭示了miRNA复杂性的一个新层面，其调节果蝇对全身性真菌感染的反应。
