title: miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster.
abstract: 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 Gal80ts-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.
authors.affiliation: Laboratory for Comparative Genomics and Bioinformatics and Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China; and.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Li
authors.affiliation: Laboratory for Comparative Genomics and Bioinformatics and Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China; and.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory for Comparative Genomics and Bioinformatics and Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China; and.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Laboratory for Comparative Genomics and Bioinformatics and Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China; and.
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, College of Life Science, Nanjing Normal University, Nanjing, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Chen
authors.affiliation: Laboratory for Comparative Genomics and Bioinformatics and Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China; and mafei01@tsinghua.org.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000276:immunology*; D029721:Drosophila Proteins / Q000276:immunology*; D004331:Drosophila melanogaster / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D035683:MicroRNAs / Q000276:immunology*; D011485:Protein Binding; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C084428:Dif protein, Drosophila; D029721:Drosophila Proteins; C586150:MIRN958 microRNA, human; D035683:MicroRNAs; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; C091227:DRS protein, Drosophila
keywords: Dif; Drosophila melanogaster; Toll; Toll signaling; miR-958