The Drosophila miR-959-962 Cluster Members Repress Toll Signaling to Regulate Antibacterial Defense during Bacterial Infection.
The Drosophila miR-959-962 Cluster Members Repress Toll Signaling to Regulate Antibacterial Defense during Bacterial Infection.
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DOI：
10.3390/ijms22020886
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发表时间：
2021-01-17
影响因子：
5.6
通讯作者：
Ma F
中科院分区：
文献类型：
--
作者：
Li R;Yao X;Zhou H;Jin P;Ma F
微小RNA（microRNAs，miRNAs）是后生动物中一类长度约为22 nt的非编码RNA分子，能够通过与mRNA转录本中的互补位点结合来下调靶基因的表达。许多单独的miRNA参与了广泛的生物学途径，但miRNA簇的功能表征是有限的。在这里，我们报告了miR-959-962簇（miR-959/960/961/962）可以减弱果蝇对细菌感染的免疫应答，这通过减少抗菌肽Drosomycin（Drs）的表达和感染后24 h内的短存活来证明。这四个miRNA成员中的每一个都被证实有助于降低果蝇的Drs表达和存活率。从机制上讲，RT-qPCR和双荧光素酶报告基因测定验证了Toll途径的关键组分管和背侧（dl）mRNA可以分别被miR-959和miR-960、miR-961和miR-962同时靶向。此外，miR-962甚至可以直接靶向Toll的3′非翻译区（UTR）。此外，在野生型果蝇中的动态表达模式分析显示，四个miRNA成员在黄体微球菌（Micrococcus luteus，M.黄体）感染。综上所述，我们的研究结果从miR-959-962簇中鉴定出四种miRNA成员作为Toll信号转导的新抑制因子，并丰富了果蝇中免疫调节miRNA的库。
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 Drosophila immune response to bacterial infection evidenced by the reduced expression of antimicrobial peptide Drosomycin (Drs) and short survival within 24 h upon infection. Each of the four miRNA members is confirmed to contribute to the reduced Drs expression and survival rate of Drosophila. Mechanically, RT-qPCR and Dual-luciferase reporter assay verify that tube and dorsal (dl) 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 Toll. In addition, the dynamic expression pattern analysis in wild-type flies reveals that four miRNA members play important functions in Drosophila immune homeostasis restoration at the late stage of Micrococcus luteus (M. luteus) 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 Drosophila.
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