MicroRNA let-7 and miR-278 regulate insect metamorphosis and oogenesis via targeting juvenile hormone early response gene Krüppel-homolog 1

Krüppel-homolog 1 (Kr-h1), a zinc finger transcription factor, transduces juvenile hormone (JH) signaling in inhibiting larval metamorphosis and promoting adult reproduction. While the transcriptional regulation of Kr-h1 has been extensively studied, little is known about its regulation at the post-transcriptional level. By using the migratory locust, Locusta migratoria as a model system, we report here that microRNA let-7 and miR-278 bound to Kr-h1 coding sequence and downregulated its expression. Application of let-7 and miR-278 agomiRs significantly reduced the level of Kr-h1 transcripts, resulting in partially precocious metamorphosis in nymphs as well as markedly decreased yolk protein precursors, arrested ovarian development and blocked oocyte maturation in adults. Moreover, the expression of let-7 and miR-278 was repressed by JH, constituting a regulatory loop of JH signaling. This study thus discovers a previously unknown mechanism by which JH suppresses the expression of let-7 and miR-278, which, together with JH induction on Kr-h1 transcription, prevents the precocious metamorphosis of nymphs and stimulates the reproduction of adult females. The results advance our understanding in the coordination of JH and miRNA regulation in insect development.