MicroRNA-133 Inhibits Behavioral Aggregation by Controlling Dopamine Synthesis in Locusts

Author Summary Phenotypic plasticity refers to the ability of an organism to alter its phenotypes in response to environmental changes. Genetic factors, such as coding and non-coding RNAs, contribute to phenotypic variation. MicroRNAs (miRNAs), which are non-coding RNAs, function as post-transcriptional repressors of gene expression. Migratory locusts show remarkable phenotypic plasticity, referred to as phase transition, which is dependent on population density changes. In the present study, we elucidated the miRNA-133-mediated post-transcriptional mechanisms involved in dopamine production that result in behavioral phase changes. We found that miR-133 directly represses two genes, henna and pale, in the dopamine pathway. Administration of the miR-133 agomir decreased dopamine production and induced a behavioral shift from the gregarious to the solitary phase. Additionally, miR-133 targeted henna in the coding region and pale in the 3 ' untranslated region, possibly indicating that different mechanisms of post-transcriptional regulation by miR-133 occur in the dopamine pathway. Moreover, the rescue experiments significantly eliminated the effects of miR-133 overexpression and inhibition on the behavioral phase changes of locusts. Our results demonstrate the role of miR-133 in phenotypic plasticity in locusts, in which the miR-133 regulates behavioral changes by controlling dopamine synthesis. Phenotypic plasticity is ubiquitous and primarily controlled by interactions between environmental and genetic factors. The migratory locust, a worldwide pest, exhibits pronounced phenotypic plasticity, which is a population density-dependent transition that occurs between the gregarious and solitary phases. Genes involved in dopamine synthesis have been shown to regulate the phase transition of locusts. However, the function of microRNAs in this process remains unknown. In this study, we report the participation of miR-133 in dopamine production and the behavioral transition by negatively regulating two critical genes, henna and pale, in the dopamine pathway. miR-133 participated in the post-transcriptional regulation of henna and pale by binding to their coding region and 3 ' untranslated region, respectively. miR-133 displayed cellular co-localization with henna/pale in the protocerebrum, and its expression in the protocerebrum was negatively correlated with henna and pale expression. Moreover, miR-133 agomir delivery suppressed henna and pale expression, which consequently decreased dopamine production, thus resulting in the behavioral shift of the locusts from the gregarious phase to the solitary phase. Increasing the dopamine content could rescue the solitary phenotype, which was induced by miR-133 agomir delivery. Conversely, miR-133 inhibition increased the expression of henna and pale, resulting in the gregarious-like behavior of solitary locusts; this gregarious phenotype could be rescued by RNA interference of henna and pale. This study shows the novel function and modulation pattern of a miRNA in phenotypic plasticity and provides insight into the underlying molecular mechanisms of the phase transition of locusts.