Reannotation of the ABCC transporters reveals a miR-980-BdABCC1 regulatory axis driving avermectin tolerance in Bactrocera dorsalis.
The oriental fruit fly Bactrocera dorsalis is a globally invasive pest with increasing insecticide resistance that threatens sustainable crop production. ATP-binding cassette (ABC) transporters are key mediators of xenobiotic detoxification, but the molecular and regulatory basis of ABCC-type transporters in this species remains unclear. Here, we present the first systematic reannotation and functional analysis of the ABCC gene family in B. dorsalis and identify a novel post-transcriptional regulatory pathway involving miR-980. Using updated genomic and transcriptomic resources, we accurately annotated eight BdABCC genes with conserved nucleotide-binding (NBD) and transmembrane domains (TMD) and strong phylogenetic conservation with dipteran homologs. Spatiotemporal expression profiling showed constitutive expression across development, elevated transcription in the midgut, Malpighian tubules and fat body, and transcriptional responsiveness of several members, particularly BdABCC1, BdABCC2, BdABCC4, and BdABCC6, to multiple insecticides. RNA interference and MK-571 inhibition demonstrated that BdABCC1 contributes to avermectin tolerance. Furthermore, luciferase reporter assays, RNA pull-down and fluorescence in situ hybridization confirmed that miR-980 directly targets the BdABCC1 coding sequence, with miR-980 overexpression suppressing BdABCC1 and increasing avermectin-induced mortality. Together, these findings identify a previously uncharacterized miR-980-BdABCC1 regulatory axis that modulates avermectin tolerance and highlights post-transcriptional regulation of ABC transporters as a potential molecular target for future RNAi-based pest management strategies.