Geng Shang, Zheng Weiwei, Zhao Yan, Xu Tianjun
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
iScience. 2022 Nov 22;25(12):105646. doi: 10.1016/j.isci.2022.105646. eCollection 2022 Dec 22.
N6-methyladenosine (mA), the most abundant internal mRNA modification in eukaryotes, plays a vital role in regulating innate immunity. However, its underlying mechanism remains largely unknown, especially in lower vertebrates. The results of the present study show that fat-mass- and obesity-associated protein (FTO), also known as a mA demethylase, improved the innate immunity and prevented and infection in miiuy croaker. Significantly, FTO-promoted immunity was dependent on its mA demethylase activity. In terms of mechanism, NOD1 has abundant methylation modification in its CDS and 3'UTR regions, and FTO can reduce its methylation level, thus avoiding its degradation by YTHDF2. In summary, our results indicate that the FTO-mediated mA modification in NOD1 mRNA promotes innate immunity by activating the NOD-like receptor pathway, which provides a molecular mechanism for the regulation of immune response via RNA methylation in teleost.
N6-甲基腺嘌呤（m⁶A）是真核生物中最丰富的内部mRNA修饰，在调节先天免疫中起着至关重要的作用。然而，其潜在机制在很大程度上仍不清楚，尤其是在低等脊椎动物中。本研究结果表明，脂肪量和肥胖相关蛋白（FTO），也被称为一种m⁶A去甲基化酶，可改善先天免疫，并预防和感染大黄鱼。值得注意的是，FTO促进的免疫依赖于其m⁶A去甲基化酶活性。在机制方面，NOD1在其编码区（CDS）和3'非翻译区（3'UTR）有丰富的甲基化修饰，FTO可以降低其甲基化水平，从而避免其被YTHDF2降解。总之，我们的结果表明，FTO介导的NOD1 mRNA中的m⁶A修饰通过激活NOD样受体途径促进先天免疫，这为硬骨鱼通过RNA甲基化调节免疫反应提供了一种分子机制。
