title: A long noncoding RNA mediates both activation and repression of immune response genes.
abstract: An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRNA-Cox2, mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of lincRNA-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of lincRNA-Cox2 as a broad-acting regulatory component of the circuit that controls the inflammatory response.
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Carpenter
authors.forename: Daniel
authors.initials: D
authors.lastname: Aiello
authors.forename: Maninjay K
authors.initials: MK
authors.lastname: Atianand
authors.forename: Emiliano P
authors.initials: EP
authors.lastname: Ricci
authors.forename: Pallavi
authors.initials: P
authors.lastname: Gandhi
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Hall
authors.forename: Meg
authors.initials: M
authors.lastname: Byron
authors.forename: Brian
authors.initials: B
authors.lastname: Monks
authors.forename: Meabh
authors.initials: M
authors.lastname: Henry-Bezy
authors.forename: Jeanne B
authors.initials: JB
authors.lastname: Lawrence
authors.forename: Luke A J
authors.initials: LA
authors.lastname: O'Neill
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Caffrey
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018448:Models, Immunological; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D062085:RNA, Long Noncoding; D051193:Toll-Like Receptors; D014157:Transcription Factors; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
references.citation: Curr Opin Cell Biol. 1999 Jun;11(3):363-71
references.pmid: 10395553
references.citation: J Immunol. 2005 Jul 1;175(1):523-30
references.pmid: 15972688
references.citation: Annu Rev Biochem. 2012;81:145-66
references.pmid: 22663078
references.citation: Nat Biotechnol. 2010 May;28(5):503-10
references.pmid: 20436462
references.citation: Nat Rev Immunol. 2009 Oct;9(10):692-703
references.pmid: 19859064
references.citation: Nat Methods. 2008 Jul;5(7):621-8
references.pmid: 18516045
references.citation: Nature. 2009 Mar 12;458(7235):223-7
references.pmid: 19182780
references.citation: Mol Biol Cell. 2008 Jul;19(7):3008-19
references.pmid: 18480411
references.citation: Dev Cell. 2010 Sep 14;19(3):469-76
references.pmid: 20833368
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11667-72
references.pmid: 19571010
references.citation: mBio. 2010 Oct 26;1(5):
references.pmid: 20978541
references.citation: Cell. 2010 Aug 6;142(3):409-19
references.pmid: 20673990
references.citation: Nature. 2007 Jun 14;447(7146):799-816
references.pmid: 17571346
references.citation: Cell. 1996 Jun 28;85(7):963-72
references.pmid: 8674124
references.citation: Ann N Y Acad Sci. 2008 Nov;1143:1-20
references.pmid: 19076341
references.citation: Nat Protoc. 2012 Jul 26;7(8):1534-50
references.pmid: 22836135
references.citation: Clin Immunol. 2009 Jan;130(1):7-15
references.pmid: 18964303
references.citation: Genes Dev. 2011 Dec 15;25(24):2573-8
references.pmid: 22155924
references.citation: Cell. 2013 Feb 14;152(4):743-54
references.pmid: 23415224
references.citation: Cell. 2009 Jul 10;138(1):129-45
references.pmid: 19596240
references.citation: Nat Immunol. 2012 Oct;13(10):916-24
references.pmid: 22990889
references.citation: Cell. 2011 Nov 11;147(4):789-802
references.pmid: 22056041
references.citation: Nature. 2012 Feb 15;482(7385):339-46
references.pmid: 22337053
references.citation: Science. 2009 Apr 10;324(5924):218-23
references.pmid: 19213877
references.citation: J Biol Chem. 2004 Mar 19;279(12):11236-43
references.pmid: 14722087
references.citation: PLoS One. 2008 Jul 30;3(7):e2803
references.pmid: 18665230
references.citation: Genomics. 2009 Apr;93(4):291-8
references.pmid: 19071207
references.citation: J Immunol. 2012 Sep 1;189(5):2084-8
references.pmid: 22851706
references.citation: Cell. 2012 Jul 20;150(2):279-90
references.pmid: 22817891
references.citation: Science. 2005 May 20;308(5725):1149-54
references.pmid: 15790807