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长链非编码 RNA TARL 通过抑制 TAK1 的下调促进 Miichthys miiuy 的抗菌活性并防止细菌逃逸。

Long noncoding RNA TARL promotes antibacterial activity and prevents bacterial escape in Miichthys miiuy through suppression of TAK1 downregulation.

机构信息

Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China.

Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai, 201306, China.

出版信息

Sci China Life Sci. 2023 Jun;66(6):1340-1357. doi: 10.1007/s11427-022-2254-6. Epub 2023 Feb 2.

Abstract

Noncoding RNA (ncRNA) is an important regulatory factor that plays a major role in innate immunity. However, most studies on ncRNA have focused on mammals, resulting in a knowledge gap on ncRNA in lower vertebrates such as teleost fish. In this study, we identified a new long noncoding RNA (lncRNA), termed TAK1-related lncRNA (TARL), which can play a positive role in the antibacterial immunity of Miichthys miiuy to Vibrio anguillarum and V. harveyi. We also found a novel microRNA miR-2188-3p that could target TAK1 and inhibit the host antibacterial response and promote bacterial escape. We further found that the antibacterial effect inhibited by miR-2188-3p could be reversed with TARL. Moreover, V. anguillarum and V. harveyi are the two most susceptible Gram-negative pathogens of aquaculture fish, and the economic losses caused by these two bacteria are immeasurable every year. This study is the first to report on the ability of lncRNA to prevent the escape of V. anguillarum and V. harveyi in fish through the competing endogenous RNA (ceRNA) mechanism. Our results not only elucidate the ceRNA mechanism of the lncRNA in antibacterial immune responses but also provide new insights into the impact of lncRNA on host immunity and bacterial escape.

摘要

非编码 RNA(ncRNA)是一种重要的调节因子,在先天免疫中发挥着主要作用。然而,大多数关于 ncRNA 的研究都集中在哺乳动物上,导致对鱼类等低等脊椎动物的 ncRNA 知之甚少。在这项研究中,我们鉴定了一种新的长非编码 RNA(lncRNA),称为 TAK1 相关 lncRNA(TARL),它可以在 Miichthys miiuy 对鳗弧菌和哈维氏弧菌的抗菌免疫中发挥积极作用。我们还发现了一种新的 microRNA miR-2188-3p,它可以靶向 TAK1 并抑制宿主的抗菌反应,促进细菌逃逸。我们进一步发现,miR-2188-3p 抑制的抗菌作用可以被 TARL 逆转。此外,鳗弧菌和哈维氏弧菌是水产养殖鱼类最易感染的两种革兰氏阴性病原体,每年由这两种细菌造成的经济损失是不可估量的。本研究首次报道了 lncRNA 通过竞争性内源性 RNA(ceRNA)机制防止鱼类中鳗弧菌和哈维氏弧菌逃逸的能力。我们的研究结果不仅阐明了 lncRNA 在抗菌免疫反应中的 ceRNA 机制,还为 lncRNA 对宿主免疫和细菌逃逸的影响提供了新的见解。

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