Jain Shanu, Shrinet Jatin, Tridibes Adak, Bhatnagar Raj K, Sunil Sujatha
Insect Resistance Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
National Institute of Malaria Research, Dwarka, New Delhi-110077, India.
Noncoding RNA. 2015 Nov 19;1(3):222-245. doi: 10.3390/ncrna1030222.
Blood feeding in initiates a cascade of events that modulate several physiological functions in the mosquito. The midgut epithelium activates several of its molecules, most important among these being microRNAs, which regulate some of the physiological changes by targeting diverse mRNAs. The present study was conducted to identify and evaluate interactions between targets of eight miRNAs that are regulated on blood feeding. Identified from our previous study, we show these eight miRNAs exhibited distinct tissue specific expression. Targets of these miRNAs were predicted using computational approaches involving bioinformatics, co-expression analysis of the transcriptome and miRNome of blood-fed midgut. Using degradome sequencing, we identified some cleaved mRNAs of these microRNAs and, by using antagomiR knockdown technology to repress the miRNAs, the targets were validated in an cell line and in mosquitoes. In-depth analysis of predicted and identified targets revealed that the regulated miRNAs modulate well-characterized molecules that are involved in combating oxidative stress and immunity pathways through a dynamic miRNA:mRNA network. Our study is the first to identify miRNA:mRNA interactomes that play important role in maintaining redox homeostasis during blood feeding in the midgut of .
吸血引发了一系列事件,这些事件调节蚊子的多种生理功能。中肠上皮细胞激活其多种分子,其中最重要的是微小RNA,它们通过靶向不同的信使核糖核酸来调节一些生理变化。本研究旨在识别和评估八种在吸血时被调控的微小RNA的靶标之间的相互作用。从我们之前的研究中识别出来的,我们发现这八种微小RNA表现出不同的组织特异性表达。使用涉及生物信息学、吸血中肠转录组和微小RNA组的共表达分析等计算方法预测了这些微小RNA的靶标。通过降解组测序,我们鉴定了这些微小RNA的一些切割后的信使核糖核酸,并且通过使用抗微小RNA敲低技术来抑制这些微小RNA,在细胞系和蚊子中验证了靶标。对预测和鉴定出的靶标的深入分析表明,受调控的微小RNA通过动态的微小RNA:信使核糖核酸网络调节参与对抗氧化应激和免疫途径的特征明确的分子。我们的研究首次鉴定了在蚊子中肠吸血过程中维持氧化还原稳态起重要作用的微小RNA:信使核糖核酸相互作用组。