A circular RNA circ_0000115 in response to graphene oxide in nematodes

Circular RNAs (circRNAs) play important roles in regulating various biological processes; however, their roles in regulating the toxicity of engineered nanomaterials (ENMs) are still unclear. Based on Illumina HiSeq2500 sequencing, we here identified 43 dysregulated circRNAs in graphene oxide (GO) (1 mg L^-1) exposed nematodes. Five of these candidate circRNAs could be further dysregulated by GO exposure in the range of μg L^-1. Using the RNA interference (RNAi) technique, we found that the alteration in expressions of circ_0000115, circ_0000247, and circ_0000665 mediated a protective response to GO exposure; however, the alteration in expressions of circ_0000201 and circ_0000308 mediated the toxicity induction of GO. In nematodes, the circ_0000115 acted in certain tissues (intestine and neurons) to regulate GO toxicity. Moreover, an intermediate filament protein IFC-2 required for intestinal development was identified as a target of circ_0000115 in regulating the GO toxicity. In the intestine, intestinal IFC-2 acted further upstream of FOXO transcriptional factor DAF-16 in the insulin signaling pathway to regulate the GO toxicity. Therefore, intestinal circ_0000115 in the signaling cascade of circ_0000115-IFC-2-DAF-16 regulates the GO toxicity by modulating the function of IFC-2.