A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation.
A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation.
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DOI：
10.1016/j.cell.2016.05.075
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发表时间：
2016-06-16
期刊：
影响因子：
64.5
通讯作者：
Fitzgerald KA
中科院分区：
文献类型：
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作者：
Atianand MK;Hu W;Satpathy AT;Shen Y;Ricci EP;Alvarez-Dominguez JR;Bhatta A;Schattgen SA;McGowan JD;Blin J;Braun JE;Gandhi P;Moore MJ;Chang HY;Lodish HF;Caffrey DR;Fitzgerald KA
长基因间非编码rna （lincRNA）是基因表达的重要调控因子。尽管lincRNAs在免疫细胞中表达，但它们在免疫中的功能在很大程度上尚未被探索。在这里，我们鉴定了一种免疫调节的lincRNA，即lincRNA- eps，它在巨噬细胞中被精确调节以控制免疫反应基因（IRGs）的表达。对lincRNA- eps缺陷小鼠巨噬细胞的转录组分析，结合功能获得和挽救实验，揭示了该lincRNA在抑制IRG表达中的特定作用。与此一致的是，lincrna - eps缺陷小鼠在体内内毒素攻击后表现出增强的炎症和致死性。lincRNA-EPS与IRGs调控区域的染色质结合，控制核小体定位和抑制转录。此外，lincRNA-EPS通过位于其3 '端的CANACA基序与异质核核糖核蛋白L相互作用来介导这些作用。总之，这些发现确定了lincRNA-EPS是炎症反应的抑制因子，突出了lincrna在免疫系统中的重要性。
Long intergenic noncoding RNAs (lincRNA) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS associates with chromatin at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3′ end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses highlighting the importance of lincRNAs in the immune system.