The Drosophila miR-959-962 Cluster Members Repress Toll Signaling to Regulate Antibacterial Defense during Bacterial Infection

MicroRNAs (miRNAs) are a class of ~22 nt non-coding RNA molecules in metazoans capable of down-regulating target gene expression by binding to the complementary sites in the mRNA transcripts. Many individual miRNAs are implicated in a broad range of biological pathways, but functional characterization of miRNA clusters in concert is limited. Here, we report that miR-959-962 cluster (miR-959/960/961/962) can weaken immune response to bacterial infection evidenced by the reduced expression of antimicrobial peptide ( ) and short survival within 24 h upon infection. Each of the four miRNA members is confirmed to contribute to the reduced expression and survival rate of . Mechanically, RT-qPCR and Dual-luciferase reporter assay verify that and ( ) mRNAs, key components of Toll pathway, can simultaneously be targeted by miR-959 and miR-960, miR-961, and miR-962, respectively. Furthermore, miR-962 can even directly target to the 3' untranslated region (UTR) of . In addition, the dynamic expression pattern analysis in wild-type flies reveals that four miRNA members play important functions in immune homeostasis restoration at the late stage of ( ) infection. Taken together, our results identify four miRNA members from miR-959-962 cluster as novel suppressors of Toll signaling and enrich the repertoire of immune-modulating miRNA in .