MiR-2b-2-5p regulates lipid metabolism and reproduction by targeting <i>CREB</i> in <i>Bactrocera dorsalis</i>

In female animals, metabolic homoeostasis and reproductive fitness are critical to population expansion. The trade-off between lipid storage and reproduction inevitably occurs. However, most studies have focused on the complex network of relationships between reproductive and metabolic physiology at the transcriptional level. In this study, we identified a microRNA, miR-2b-2-5p, in a highly invasive quarantine pest, <i>Bactrocera dorsalis</i>. Knockdown of miR-2b-2-5p by antagomiR microinjection impaired ovarian development, reduced fecundity, and decreased triglyceride (TAG) storage in the fat body, whereas overexpression of miR-2b-2-5p by injection of its mimic caused reproductive defects similar to knockdown but increased TAG. Bioinformatics analysis and dual luciferase assay indicated that cyclic AMP response element (CRE)-binding protein (CREB) was the target gene of miR-2b-2-5p. RNAi-mediated knockdown of <i>CREB</i> led to excessive lipid storage and reproductive defects. Further starvation treatment revealed that miR-2b-2-5p functions by fine-tuning <i>CREB</i> expression in response to dietary stimuli. These results suggest that miR-2b-2-5p acts as a monitor to regulate <i>CREB</i> mRNA levels in the fat body, maintaining lipid homoeostasis and keeping the reproductive system on track. Thus, our study not only provides new insights into the interaction between metabolism and reproduction at the posttranscriptional level in <i>B. dorsalis</i>, but also providing a potential eco-friendly control strategy (RNAi-based biopesticides targeting essential miRNAs) for this notorious agricultural pest.