The 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 .