Mulberry-derived miR168a downregulates BmMthl1 to promote physical development and fecundity in silkworms

Plant-derived miRNAs and their interactions with host organisms are considered important factors in regulating host physiological processes. In this study, we investigated the interaction between the silkworm, an oligophagous insect, and its primary food source, mulberry, to determine whether mulberry-derived miRNAs can penetrate silkworm cells and regulate their functions. Our results demonstrated that miR168a from mulberry leaves enters the silkworm hemolymph and binds to the silkworm Argonaute1 BmAGO1, which is transported via vesicles secreted by silkworm cells to exert its regulatory functions. In vivo and in vitro functional studies revealed that miR168a targets the mRNA of silkworm G protein-coupled receptor, BmMthl1, thereby inhibiting its expression and activating the JNK-FoxO pathway. This activation reduces oxidative stress responses, prolongs the lifespan of silkworms, and improves their reproductive capacity. These findings highlight the challenges of replacing mulberry leaves with alternative protein sources and provide a foundation for developing silkworm germplasms suitable for factory rearing.