Screening of microRNAs controlling body fat in Drosophila melanogaster and identification of miR-969 and its target, Gr47b

MicroRNAs (miRNAs) are small non-protein coding RNAs and post-transcriptionally regulate cellular gene expression. In animal development, miRNAs play essential roles such as stem cell maintenance, organogenesis, and apoptosis. Using gain-of-function (GOF) screening with 160 miRNA lines in Drosophila melanogaster, we identified a set of miRNAs which regulates body fat contents and named them microCATs (microRNAs Controlling Adipose Tissue). Further examination of egg-to-adult developmental kinetics of selected miRNA lines showed a negative correlation between fat content and developmental time. Comparison of microCATs with loss-of-function miRNA screening data uncovered miR-969 as an essential regulator of adiposity. Subsequently, we demonstrated adipose tissue-specific knock-down of gustatory receptor 47b (Gr47b), a miR-969 target, greatly reduced the amount of body fat, recapitulating the miR-969 GOF phenotype.微小RNA（MicroRNAs，miRNAs）是一类小型非编码RNA，可在转录后水平调控细胞基因的表达。在动物发育过程中，miRNA发挥着不可或缺的重要作用，涵盖干细胞维持、器官发生以及细胞凋亡等环节。本研究通过对黑腹果蝇（Drosophila melanogaster）的160株miRNA品系开展功能获得性（gain-of-function，GOF）筛选，鉴定出一组可调控体脂含量的miRNA，并将其命名为microCATs（调控脂肪组织的微小RNA，microRNAs Controlling Adipose Tissue）。对筛选得到的miRNA品系进行卵至成虫发育动力学分析后发现，体脂含量与发育时长呈显著负相关关系。将microCATs与功能丧失性（loss-of-function）miRNA筛选数据进行比对后，成功鉴定出miR-969为体脂状态的关键调控因子。后续实验证实，对miR-969的靶基因味觉受体47b（Gr47b）进行脂肪组织特异性敲低，可显著降低体脂含量，完整重现了miR-969功能获得性的表型。