Zhou Hongjian, Ni Jiajia, Wu Shanshan, Ma Fei, Jin Ping, Li Shengjie
Laboratory for Comparative Genomics and Bioinformatics & Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, PR China.
Jiangsu Provincial Key Construction Laboratory of Special Biomass Byproduct Resource Utilization, School of Food Science, Nanjing Xiaozhuang University, Nanjing, 211171, PR China.
Dev Comp Immunol. 2021 Nov;124:104183. doi: 10.1016/j.dci.2021.104183. Epub 2021 Jun 24.
The Toll signaling pathway is highly conserved from insects to mammals. Drosophila is a model species that is commonly used to study innate immunity. Although many studies have assessed protein-coding genes that regulate the Toll pathway, it is unclear whether long noncoding RNAs (lncRNAs) play regulatory roles in the Toll pathway. Here, we evaluated the expression of the lncRNA CR46018 in Drosophila. Our results showed that this lncRNA was significantly overexpressed after infection of Drosophila with Micrococcus luteus. A CR46018-overexpressing Drosophila strain was then constructed; we expected that CR46018 overexpression would enhance the expression of various antimicrobial peptides downstream of the Toll pathway, regardless of infection with M. luteus. RNA-seq analysis of CR46018-overexpressing Drosophila after infection with M. luteus showed that upregulated genes were mainly enriched in Toll and Imd signaling pathways. Moreover, bioinformatics predictions and RNA-immunoprecipitation experiments showed that CR46018 interacted with the transcription factors Dif and Dorsal to enhance the Toll pathway. During gram-positive bacterial infection, flies overexpressing CR46018 showed favorable survival compared with flies in the control group. Overall, our current work not only reveals a new immune regulatory factor, lncRNA-CR46018, and explores its potential regulatory model, but also provides a new perspective for the effect of immune disorders on the survival of Drosophila melanogaster.
Toll信号通路从昆虫到哺乳动物都高度保守。果蝇是常用于研究先天免疫的模式物种。尽管许多研究评估了调控Toll通路的蛋白质编码基因，但尚不清楚长链非编码RNA（lncRNA）是否在Toll通路中发挥调控作用。在此，我们评估了果蝇中lncRNA CR46018的表达。我们的结果表明，在用藤黄微球菌感染果蝇后，这种lncRNA显著过表达。随后构建了过表达CR46018的果蝇品系；我们预期，无论是否感染藤黄微球菌，CR46018的过表达都会增强Toll通路下游各种抗菌肽的表达。对感染藤黄微球菌后的过表达CR46018的果蝇进行RNA测序分析表明，上调的基因主要富集在Toll和Imd信号通路中。此外，生物信息学预测和RNA免疫沉淀实验表明，CR46018与转录因子Dif和Dorsal相互作用以增强Toll通路。在革兰氏阳性菌感染期间，与对照组果蝇相比，过表达CR46018的果蝇表现出更好的存活率。总体而言，我们目前的工作不仅揭示了一种新的免疫调节因子lncRNA-CR46018，并探索了其潜在的调控模式，还为免疫紊乱对黑腹果蝇存活的影响提供了新的视角。
