LncRNA-CR11538 Decoys Dif/Dorsal to Reduce Antimicrobial Peptide Products for Restoring Drosophila Toll Immunity Homeostasis.
LncRNA-CR11538 Decoys Dif/Dorsal to Reduce Antimicrobial Peptide Products for Restoring Drosophila Toll Immunity Homeostasis.
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LncRNA-CR11538 诱骗 Dif/Dorsal 以减少抗菌肽产品，以恢复果蝇 Toll 免疫稳态
DOI：
10.3390/ijms221810117
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发表时间：
2021-09-18
影响因子：
5.6
通讯作者：
Ma F
中科院分区：
文献类型：
--
作者：
Zhou H;Li S;Wu S;Jin P;Ma F
避免过度或不足的免疫反应以及维持体内平衡对于动物生存至关重要。尽管许多参与免疫反应的正向或负向调节剂已被识别，但迄今为止关于长非编码RNA（lncRNA）是否可以调节果蝇免疫反应的报道很少。在本研究中，我们首次发现lncRNA-CR11538的过表达可以抑制体内抗菌肽Drosomycin（Drs）和Metchnikowin（Mtk）的表达，从而抑制Toll信号通路。其次，我们的结果表明，基于亚细胞定位和 RIP 分析，lncRNA-CR11538 可以与细胞核中的转录因子 Dif/Dorsal 相互作用。第三，我们的研究结果表明，通过 ChIP-qPCR 和双荧光素酶报告实验，lncRNA-CR11538 可以诱使 Dif/Dorsal 远离 Drs 和 Mtk 的启动子，从而抑制它们的转录。第四，野生型果蝇（w1118）在藤黄杆菌刺激后不同时间点Drs、Dif、Dorsal和lncRNA-CR11538的动态表达变化揭示了lncRNA-CR11538可以帮助果蝇在免疫反应后期恢复免疫稳态。总的来说，我们的研究揭示了lncRNA-CR11538作为Dif/Dorsal诱饵下调抗菌肽表达以恢复果蝇Toll免疫稳态的新机制，并为进一步研究动物先天免疫的复杂调节机制提供了新的见解。
Avoiding excessive or insufficient immune responses and maintaining homeostasis are critical for animal survival. Although many positive or negative modulators involved in immune responses have been identified, little has been reported to date concerning whether the long non-coding RNA (lncRNA) can regulate Drosophila immunity response. In this study, we firstly discover that the overexpression of lncRNA-CR11538 can inhibit the expressions of antimicrobial peptides Drosomycin (Drs) and Metchnikowin (Mtk) in vivo, thereby suppressing the Toll signaling pathway. Secondly, our results demonstrate that lncRNA-CR11538 can interact with transcription factors Dif/Dorsal in the nucleus based on both subcellular localization and RIP analyses. Thirdly, our findings reveal that lncRNA-CR11538 can decoy Dif/Dorsal away from the promoters of Drs and Mtk to repress their transcriptions by ChIP-qPCR and dual luciferase report experiments. Fourthly, the dynamic expression changes of Drs, Dif, Dorsal and lncRNA-CR11538 in wild-type flies (w1118) at different time points after M. luteus stimulation disclose that lncRNA-CR11538 can help Drosophila restore immune homeostasis in the later period of immune response. Overall, our study reveals a novel mechanism by which lncRNA-CR11538 serves as a Dif/Dorsal decoy to downregulate antimicrobial peptide expressions for restoring Drosophila Toll immunity homeostasis, and provides a new insight into further studying the complex regulatory mechanism of animal innate immunity.
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影响因子：
4.6
作者：
Jenny, Andreas;Hachet, Olivier;Ephrussi, Anne
通讯作者：
Ephrussi, Anne
影响因子：
64.8
作者：
通讯作者：
--
Pellino 的细胞表面定位通过控制果蝇中 MyD88 的周转来拮抗 Toll 介导的先天免疫信号
影响因子：
16.6
作者：
Ji, Shanming;Sun, Ming;Zheng, Xiudeng;Li, Lin;Sun, Liwei;Chen, Dahua;Sun, Qinmiao
通讯作者：
Sun, Qinmiao
影响因子：
14.9
作者：
Nguyen D;Krueger BJ;Sedore SC;Brogie JE;Rogers JT;Rajendra TK;Saunders A;Matera AG;Lis JT;Uguen P;Price DH
通讯作者：
Price DH
影响因子：
30.8
作者：
Herzog, Veronika A.;Lempradl, Adelheid;Trupke, Johanna;Okulski, Helena;Altmutter, Christina;Ruge, Frank;Boidol, Bernd;Kubicek, Stefan;Schmauss, Gerald;Aumayr, Karin;Ruf, Marius;Pospisilik, Andrew;Dimond, Andrew;Senergin, Hasene Basak;Vargas, Marcus L.;Simon, Jeffrey A.;Ringrose, Leonie
通讯作者：
Ringrose, Leonie