A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation

被引：388

作者：

Atianand, Maninjay K. ^{[1
]}

Hu, Wenqian ^{[2
,8
]}

Satpathy, Ansuman T. ^{[3
,4
]}

Shen, Ying ^{[3
,4
]}

Ricci, Emiliano P. ^{[5
,6
,9
]}

Alvarez-Dominguez, Juan R. ^{[2
]}

Bhatta, Ankit ^{[1
]}

Schattgen, Stefan A. ^{[1
]}

McGowan, Jason D. ^{[1
]}

Blin, Juliana ^{[1
]}

Braun, Joerg E. ^{[5
,6
]}

Gandhi, Pallavi ^{[1
]}

Moore, Melissa J. ^{[5
,6
]}

Chang, Howard Y. ^{[3
,4
]}

Lodish, Harvey F. ^{[2
]}

Caffrey, Daniel R. ^{[1
]}

Fitzgerald, Katherine A. ^{[1
,7
]}

机构：

[1] Univ Massachusetts, Sch Med, Program Innate Immun, Worcester, MA 01605 USA

[2] MIT, Whitehead Inst, Cambridge, MA 02142 USA

[3] Stanford Univ, Sch Med, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA

[5] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01655 USA

[6] Univ Massachusetts, Sch Med, Dept Biochem & Pharmacol, Worcester, MA 01655 USA

[7] NTNU, Ctr Mol Inflammat Res, Dept Canc Res & Mol Med, N-7491 Trondheim, Norway

[8] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA

[9] Univ Lyon, Ecole Normale Super Lyon, Ctr Int Rech Infectiol, F-69364 Lyon, France

来源：

CELL | 2016年 / 165卷 / 07期

关键词：

CHROMATIN SITES; EXPRESSION; SUSCEPTIBILITY; ACTIVATION; REPRESSION; EVOLUTION; REVEALS; DISEASE; REGIONS; HNRNPL;

D O I：

10.1016/j.cell.2016.05.075

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Long intergenic noncoding RNAs (lincRNAs) 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 localizes 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.

引用

页码：1672 / 1685

页数：14

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