Lu Yajing, Liu Xu, Xie Minghong, Liu Mingjia, Ye Mengling, Li Mingxuan, Chen Xian-Ming, Li Xiaoqing, Zhou Rui
Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China.
Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China.
J Immunol. 2017 Nov 15;199(10):3571-3582. doi: 10.4049/jimmunol.1700091. Epub 2017 Oct 9.
Long noncoding RNAs, a newly identified class of noncoding RNAs, are important regulators of gene expression in innate immunity. We report in this study that the transcription of FIRRE, a conserved long noncoding RNA between humans and mice, is controlled by NF-κB signaling in macrophages and intestinal epithelial cells. Functionally, FIRRE appears to positively regulate the expression of several inflammatory genes in macrophages or intestinal epithelial cells in response to LPS stimulation via posttranscriptional mechanisms. Specifically, FIRRE physically interacts with heterogeneous nuclear ribonucleoproteins U, regulating the stability of mRNAs of selected inflammatory genes through targeting the AU-rich elements of their mRNAs in cells following LPS stimulation. Therefore, our data indicate a new regulatory role for NF-κB-responsive FIRRE in the posttranscriptional regulation of inflammatory genes in the innate immune system.
长链非编码RNA是一类新发现的非编码RNA，是先天免疫中基因表达的重要调节因子。我们在本研究中报告，FIRRE是人和小鼠之间保守的长链非编码RNA，其转录受巨噬细胞和肠上皮细胞中NF-κB信号通路的控制。在功能上，FIRRE似乎通过转录后机制在巨噬细胞或肠上皮细胞中对LPS刺激作出反应，正向调节几种炎症基因的表达。具体而言，FIRRE与不均一核核糖核蛋白U发生物理相互作用，通过在LPS刺激后靶向细胞中选定炎症基因mRNA的富含AU元件，调节其mRNA的稳定性。因此，我们的数据表明NF-κB反应性FIRRE在先天免疫系统炎症基因的转录后调控中具有新的调节作用。
