期刊
PLOS GENETICS
卷 18, 期 10, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1010418
关键词
-
资金
- National Key R&D Program of China [2019YFD1002100]
- China Agriculture Research System of MOF and MARA [CARS-26]
Increasing evidence suggests that miRNAs play important regulatory roles in insect physiological processes, including energy metabolism. This study found that the miR-275/305 cluster is crucial for maintaining energy metabolic homeostasis in Bactrocera dorsalis. miR-275 and miR-305 were shown to repress the expression of SLC2A1 and GLIS2, respectively, through binding to their 3'UTR regions. These findings contribute to our understanding of metabolic adaptation to different dietary stimulations and provide insights into potential targets of important miRNAs in non-model organisms.
Increasing evidence indicates that miRNAs play crucial regulatory roles in various physiological processes of insects, including systemic metabolism. However, the molecular mechanisms of how specific miRNAs regulate energy metabolic homeostasis remain largely unknown. In the present study, we found that an evolutionarily conserved miR-275/305 cluster was essential for maintaining energy metabolic homeostasis in response to dietary yeast stimulation in Bactrocera dorsalis. Depletion of miR-275 and miR-305 by the CRISPR/Cas9 system significantly reduced triglyceride and glycogen contents, elevated total sugar levels, and impaired flight capacity. Combined in vivo and in vitro experiments, we demonstrated that miR-275 and miR-305 can bind to the 3'UTR regions of SLC2A1 and GLIS2 to repress their expression, respectively. RNAi-mediated knockdown of these two genes partially rescued metabolic phenotypes caused by inhibiting miR-275 and miR-305. Furthermore, we further illustrated that the miR-275/305 cluster acting as a regulator of the metabolic axis was controlled by the insulin signaling pathway. In conclusion, our work combined genetic and physiological approaches to clarify the molecular mechanism of metabolic homeostasis in response to different dietary stimulations and provided a reference for deciphering the potential targets of physiologically important miRNAs in a non-model organism. Author summary Metabolic homeostasis is critical for the fundamental physiological processes of organisms, and its dysregulation leads to severe metabolic and physiological diseases, such as obesity and insulin resistance. miRNA is a type of endogenous non-coding RNA that participates in multiple biological processes directly or indirectly. In the present study, we found the involvement of the miR-275/305 cluster in energy metabolism in female B. dorsalis and revealed the related post-transcriptional regulatory mechanisms. The miR-275/305 cluster expression positively responded to dietary yeast stimulation, and its knockdown had a profound impact on the triglyceride, glycogen, and glucose metabolisms at the adult stage of B. dorsalis. Furthermore, we uncovered that the miR-275/305 cluster mainly functions through negatively regulating the transcription of the SLC2A1/GLIS2, eventually ensuring normal metabolic physiology. Further, this miRNA-target axis was under the control of the conserved insulin signaling pathway. Therefore, our findings provide novel insight into the molecular basis of the metabolic adaptation to nutrient availability in B. dorsalis.
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