title: miR-34 Modulates Innate Immunity and Ecdysone Signaling in Drosophila.
abstract: microRNAs are endogenous small regulatory RNAs that modulate myriad biological processes by repressing target gene expression in a sequence-specific manner. Here we show that the conserved miRNA miR-34 regulates innate immunity and ecdysone signaling in Drosophila. miR-34 over-expression activates antibacterial innate immunity signaling both in cultured cells and in vivo, and flies over-expressing miR-34 display improved survival and pathogen clearance upon Gram-negative bacterial infection; whereas miR-34 knockout animals are defective in antibacterial defense. In particular, miR-34 achieves its immune-stimulatory function, at least in part, by repressing the two novel target genes Dlg1 and Eip75B. In addition, our study reveals a mutual repression between miR-34 expression and ecdysone signaling, and identifies miR-34 as a node in the intricate interplay between ecdysone signaling and innate immunity. Lastly, we identify cis-regulatory genomic elements and trans-acting transcription factors required for optimal ecdysone-mediated repression of miR-34. Taken together, our study enriches the repertoire of immune-modulating miRNAs in animals, and provides new insights into the interplay between steroid hormone signaling and innate immunity.
authors.affiliation: Tumor Initiation and Maintenance Program; Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.|Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Xiong
authors.affiliation: Tumor Initiation and Maintenance Program; Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.|Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.
authors.forename: Krishna
authors.identifier: http://orcid.org/0000-0002-6523-1091
authors.initials: K
authors.lastname: Kurthkoti
authors.affiliation: Tumor Initiation and Maintenance Program; Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.|Department of Pediatrics, University of California San Diego School of Medicine, California, United States of America.
authors.forename: Kung-Yen
authors.initials: KY
authors.lastname: Chang
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, United States of America.
authors.forename: Jian-Liang
authors.identifier: http://orcid.org/0000-0002-6487-081X
authors.initials: JL
authors.lastname: Li
authors.affiliation: Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Xingjie
authors.initials: X
authors.lastname: Ren
authors.affiliation: Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Ni
authors.affiliation: Tumor Initiation and Maintenance Program; Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.|Department of Pediatrics, University of California San Diego School of Medicine, California, United States of America.
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
authors.affiliation: Tumor Initiation and Maintenance Program; Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.|Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, California, United States of America.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000276:immunology; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000276:immunology; D004331:Drosophila melanogaster / Q000276:immunology*; D004440:Ecdysone / Q000276:immunology*; D055786:Gene Knockout Techniques; D007113:Immunity, Innate / Q000276:immunology*; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000276:immunology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C570893:MIRN34 microRNA, Drosophila; D035683:MicroRNAs; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C061375:Eip75B protein, Drosophila; C070350:dlg1 protein, Drosophila; D004440:Ecdysone