Project description:Circular RNAs (circRNAs) are a new group of noncoding and regulatory RNAs that are particularly abundant in the nervous system, although their physiological functions are underexplored. Here we report that the brain-enriched circular RNA Edis (Ect4-derived immune suppressor) plays an essential role in neuronal development in Drosophila, as its depletion causes defective axonal projection of mushroom body (MB) neurons in the brain, as well as impaired locomotor activity and shortened lifespan of adult flies. In addition, we show that the castor gene, which encodes a transcription factor involved in neurodevelopment, is upregulated in Edis knockdown neurons. Notably, castor overexpression phenocopies Edis knockdown, and reducing castor levels suppresses the neuronal developmental phenotypes in Edis-depleted neurons. Furthermore, chromatin immunoprecipitation analysis reveals that the immune transcription factor Relish occupies two sites at the castor promoter, and that both sites are required for optimal castor gene activation induced by either immune challenge or Edis depletion. Lastly, Relish mutation rescues both the castor hyperactivation phenotype and neuronal defects in Edis knockdown animals. We conclude that the circular RNA Edis acts through Relish and castor to regulate neuronal development.
