Laboratory of Experimental Immunology, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
PEDEGO Research Unit, and Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
PLoS Pathog. 2019 Jan 11;15(1):e1007504. doi: 10.1371/journal.ppat.1007504. eCollection 2019 Jan.
Non-coding RNAs have important roles in regulating physiology, including immunity. Here, we performed transcriptome profiling of immune-responsive genes in Drosophila melanogaster during a Gram-positive bacterial infection, concentrating on long non-coding RNA (lncRNA) genes. The gene most highly induced by a Micrococcus luteus infection was CR44404, named Induced by Infection (lincRNA-IBIN). lincRNA-IBIN is induced by both Gram-positive and Gram-negative bacteria in Drosophila adults and parasitoid wasp Leptopilina boulardi in Drosophila larvae, as well as by the activation of the Toll or the Imd pathway in unchallenged flies. We show that upon infection, lincRNA-IBIN is expressed in the fat body, in hemocytes and in the gut, and its expression is regulated by NF-κB signaling and the chromatin modeling brahma complex. In the fat body, overexpression of lincRNA-IBIN affected the expression of Toll pathway -mediated genes. Notably, overexpression of lincRNA-IBIN in unchallenged flies elevated sugar levels in the hemolymph by enhancing the expression of genes important for glucose retrieval. These data show that lncRNA genes play a role in Drosophila immunity and indicate that lincRNA-IBIN acts as a link between innate immune responses and metabolism.
非编码 RNA 在调节生理机能方面发挥着重要作用,包括免疫。在这里,我们对革兰氏阳性菌感染的黑腹果蝇免疫应答基因进行了转录组分析,重点关注长非编码 RNA (lncRNA) 基因。受金黄色葡萄球菌感染诱导表达量最高的基因是 CR44404,被命名为感染诱导的 lincRNA-IBIN。lincRNA-IBIN 可被革兰氏阳性菌和革兰氏阴性菌诱导,也可被寄生蜂舞毒蛾在黑腹果蝇幼虫中诱导,同时还可被未受挑战的果蝇中 Toll 或 Imd 通路的激活所诱导。我们发现,在感染过程中,lincRNA-IBIN 在脂肪体、血细胞和肠道中表达,其表达受到 NF-κB 信号和染色质建模 brahma 复合物的调控。在脂肪体中,lincRNA-IBIN 的过表达影响了 Toll 通路介导的基因的表达。值得注意的是,在未受挑战的果蝇中过表达 lincRNA-IBIN 通过增强对葡萄糖摄取重要基因的表达,提高了血淋巴中的糖水平。这些数据表明 lncRNA 基因在果蝇免疫中发挥作用,并表明 lincRNA-IBIN 作为先天免疫反应和代谢之间的联系。