LncRNA-IRAR-mediated regulation of insulin receptor transcripts in Drosophila melanogaster during nutritional stress
LncRNA-IRAR-mediated regulation of insulin receptor transcripts in Drosophila melanogaster during nutritional stress
复制标题
DOI：
10.1111/imb.12756
复制
发表时间：
2022-01-03
影响因子：
2.6
通讯作者：
Qi, Guojun
中科院分区：
文献类型：
--
作者：
Chen, Jie;Huang, Yuantai;Qi, Guojun
胰岛素信号通路在调节细胞中糖、脂肪和蛋白质的代谢中起着至关重要的作用，从而影响生物体的生长、代谢、繁殖和衰老。然而，人们对长链非编码RNA（lncRNA）在应激条件下调节昆虫胰岛素受体的功能知之甚少。在这项研究中，我们表明，胰岛素受体相关的lncRNA（IRAR）调节胰岛素受体转录在营养应激反应的果蝇。CRISPR-Cas9的基因组编辑显示IRAR突变体对环境营养变化的敏感性降低。相反，在低营养下，过表达tubulin-gal4> IRAR的突变体的敏感性增加。与w1118组相比，随着胰岛素浓度的增加，IRAR突变体的化蛹和羽化时间显著延迟。此外，IRAR的表达模式与胰岛素受体的四种转录本从胚胎期到成体期的表达模式基本一致。RNA免疫沉淀实验表明，在营养胁迫下，IRAR通过与FOXO结合直接调节胰岛素受体转录。据我们所知，这是第一个研究，描述了一个模型的lncRNA介导的发展调节，通过胰岛素受体转录。
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.