IIott Nicholas E, Heward James A, Roux Benoit, Tsitsiou Eleni, Fenwick Peter S, Lenzi Luca, Goodhead Ian, Hertz-Fowler Christiane, Heger Andreas, Hall Neil, Donnelly Louise E, Sims David, Lindsay Mark A
1] CGAT Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK [2].
1] Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY Bath, UK [2].
Nat Commun. 2014 Jun 9;5:3979. doi: 10.1038/ncomms4979.
Early reports indicate that long non-coding RNAs (lncRNAs) are novel regulators of biological responses. However, their role in the human innate immune response, which provides the initial defence against infection, is largely unexplored. To address this issue, here we characterize the long non-coding RNA transcriptome in primary human monocytes using RNA sequencing. We identify 76 enhancer RNAs (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS). Crucially, we demonstrate that knockdown of nuclear-localized, NF-κB-regulated, eRNAs (IL1β-eRNA) and RBT (IL1β-RBT46) surrounding the IL1β locus, attenuates LPS-induced messenger RNA transcription and release of the proinflammatory mediators, IL1β and CXCL8. We predict that lncRNAs can be important regulators of the human innate immune response.
早期报告表明，长链非编码RNA（lncRNA）是生物反应的新型调节因子。然而，它们在人类先天免疫反应中的作用在很大程度上尚未得到探索，而先天免疫反应是针对感染的初始防御。为了解决这个问题，我们在这里使用RNA测序对原代人单核细胞中的长链非编码RNA转录组进行了表征。我们鉴定出76种增强子RNA（eRNA）、40种典型lncRNA、65种反义lncRNA以及35个双向转录区域（RBT），它们在对细菌脂多糖（LPS）的反应中差异表达。至关重要的是，我们证明了敲低IL1β基因座周围的核定位、NF-κB调节的eRNA（IL1β-eRNA）和RBT（IL1β-RBT46），会减弱LPS诱导的信使RNA转录以及促炎介质IL1β和CXCL8的释放。我们预测lncRNA可能是人类先天免疫反应的重要调节因子。
