linc-AAM Facilitates Gene Expression Contributing to Macrophage Activation and Adaptive Immune Responses
linc-AAM Facilitates Gene Expression Contributing to Macrophage Activation and Adaptive Immune Responses
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linc-AAM 促进基因表达，促进巨噬细胞激活和适应性免疫反应
DOI：
10.1016/j.celrep.2020.108584
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发表时间：
2021-01-05
期刊：
影响因子：
8.8
通讯作者：
Sun, Hongxiang
中科院分区：
文献类型：
--
作者：
Chen, Xiangfeng;He, Yanfei;Sun, Hongxiang
虽然各种长链非编码RNA（lncRNA）在活化的巨噬细胞中特异性表达，但它们的体内功能和作用机制在很大程度上未被探索。在这里，我们确定了一个长的基因间非编码RNA与激活的巨噬细胞（linc-AAM），并阐明其功能和机制。linc-AAM在活化的巨噬细胞中高度表达。体外功能分析表明，linc-AAM促进巨噬细胞活化，并促进免疫应答基因（IRGs）的表达。在机制上，linc-AAM通过两个CACACA基序与异质核核糖核蛋白L（hnRNPL）相互作用，导致其从组蛋白H3解离以激活染色质并促进IRG的转录。值得注意的是，linc-AAM敲除（KO）小鼠在体内表现出对卵清蛋白（OVA）的抗原特异性细胞和体液免疫应答受损。总之，结果揭示了lncRNA调节hnRNPL功能的机制，并证实linc-AAM作为转录增强子激活巨噬细胞并促进适应性免疫。
Although various long noncoding RNAs (lncRNAs) are specifically expressed in activated macrophages, their in vivo functions and mechanisms of action are largely unexplored. Here, we identify a long intergenic noncoding RNA associated with activated macrophage (linc-AAM) and elucidate its function and mechanisms. linc-AAM is highly expressed in activated macrophages. In vitro function analysis reveals that linc-AAM facilitates macrophage activation and promotes the expression of immune response genes (IRGs). In mechanisms, linc-AAM interacts with heterogeneous nuclear ribonucleoprotein L (hnRNPL) via two CACACA motifs, resulting in its dissociation from histone H3 to activate chromatin and facilitate transcription of IRGs. Of note, linc-AAM knockout (KO) mice manifest impaired antigen-specific cellular and humoral immune responses to ovalbumin (OVA) in vivo. Altogether, the results uncover a mechanism of lncRNA in modulating hnRNPL function and confirm that linc-AAM acts as a transcription enhancer to activate macrophages and promote adaptive immunity.