Abstract
Insects are protected from xenobiotics by multiple gene families, such as cytochrome P450s, glutathione S-transferases, UDP-glycosyltransferases (UGTs), and ATP-binding cassette (ABC) transporters. In addition to protecting against xenobiotics, some of these genes are key players in physiological homeostasis. However, how many ABCs or UGTs are required for survival is largely unknown. We investigated which ABC transporters and UGTs are required for survival using an RNAi screen of 71 genes in Drosophila melanogaster. Genes which generated a reduced number of adults after RNAi knock down were further replicated and validated using somatic CRISPR-based knockout (TKO) lines. Of the 13 genes identified by RNAi screen, we selected five which had CRISPR-based knockout lines available for validation. Of these, only one gene displayed the same lethality phenotype observed with RNAi after full knockout: CG3164, which we named vitalporter (vptr). RNAi of vitalporter prevented pupal development when initiated in embryos, prevented adult emergence when initiated in L2-L3 larvae, and shortened adult lifespan when initiated in adults. Tissue-specific RNAi suggests that the lethality of vitalporter is likely due to effects in the nervous system. Discovery of vitalporter's role in survival opens the door for further investigation into the importance of this and other ABC transporters in D. melanogaster physiology.
