LncRNA-IRAR-mediated regulation of insulin receptor transcripts in Drosophila melanogaster during nutritional stress

The insulin signalling pathway plays a crucial role in regulating the metabolism of sugars, fats and proteins in cells, thereby affecting the growth, metabolism, reproduction and ageing of organisms. However, little is known about the functions of long non-coding RNAs (lncRNAs) in the regulation of insulin receptors under stress conditions in insects. In this study, we showed that insulin receptor-associated lncRNA (IRAR) regulates insulin receptor transcripts in response to nutritional stress in Drosophila melanogaster. Genome editing by CRISPR-Cas9 showed reduced sensitivity of IRAR mutants to environmental nutritional changes. In contrast, the sensitivity of mutants overexpressing tubulin-gal4 > IRAR increased under low nutrition. The pupation and eclosion timings in IRAR mutants were significantly delayed with an increase in insulin concentration compared with that in the w1118 group. In addition, the expression pattern of IRAR was almost consistent with that of the four transcripts of the insulin receptor from the embryonic period to the adult period. RNA immunoprecipitation assay showed the direct regulation of insulin receptor transcripts by IRAR to the through FOXO binding under nutritional stress. To our knowledge, this is the first study that describes a model of lncRNA-mediated development regulation through insulin receptor transcripts.