miR-34 Modulates Innate Immunity and Ecdysone Signaling in Drosophila

PLoS Pathogens

Krishna Kurthkoti¹  Xingjie Ren¹  Rui Zhou¹  Kung-Yen Chang³  Jian-Quan Ni³  Jian-Liang Li⁶  Tariq M. Rana⁶  Xiao-Peng Xiong⁶ 

[1] 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;Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, California, United States of America;Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing, China;Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, United States of America;Tumor Initiation and Maintenance Program

关键词: MicroRNAs;    Innate immune system;    Transcription factors;    Messenger RNA;    Gene expression;    Drosophila melanogaster;    RNA isolation;    Gene regulation;   

DOI  :  10.1371/journal.ppat.1006034

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY