title: A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics.
abstract: Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of mouse lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-κB-dependent manner. Lethe, a pseudogene lncRNA, is selectively induced by proinflammatory cytokines via NF-κB or glucocorticoid receptor agonist, and functions in negative feedback signaling to NF-κB. Lethe interacts with NF-κB subunit RelA to inhibit RelA DNA binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased NF-κB activity. These findings suggest that expression of pseudogenes lncRNAs are actively regulated and constitute functional regulators of inflammatory signaling. DOI:http://dx.doi.org/10.7554/eLife.00762.001.
authors.affiliation: Program in Epithelial Biology , Howard Hughes Medical Institute, Stanford University School of Medicine , Stanford , United States.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Rapicavoli
authors.forename: Kun
authors.initials: K
authors.lastname: Qu
authors.forename: Jiajing
authors.initials: J
authors.lastname: Zhang
authors.forename: Megan
authors.initials: M
authors.lastname: Mikhail
authors.forename: Remi-Martin
authors.initials: RM
authors.lastname: Laberge
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000235:genetics*; D011544:Pseudogenes; D062085:RNA, Long Noncoding / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D062085:RNA, Long Noncoding; D014409:Tumor Necrosis Factor-alpha
keywords: Mouse; NF-κB; genomics; noncoding RNA
references.citation: Immunol Rev. 2012 Mar;246(1):205-20
references.pmid: 22435557
references.citation: Genes Dev. 2011 Sep 15;25(18):1915-27
references.pmid: 21890647
references.citation: Cell. 2013 Feb 14;152(4):743-54
references.pmid: 23415224
references.citation: Nat Immunol. 2010 May;11(5):373-84
references.pmid: 20404851
references.citation: Cell. 2007 Jun 29;129(7):1311-23
references.pmid: 17604720
references.citation: Mol Cell Biol. 2000 Nov;20(22):8602-12
references.pmid: 11046155
references.citation: Nature. 2011 Aug 28;477(7364):295-300
references.pmid: 21874018
references.citation: Nat Methods. 2010 Sep;7(9):709-15
references.pmid: 20711195
references.citation: Cell. 2011 Oct 14;147(2):344-57
references.pmid: 22000013
references.citation: Genome Res. 2008 Sep;18(9):1433-45
references.pmid: 18562676
references.citation: Mol Cell. 2011 Sep 16;43(6):904-14
references.pmid: 21925379
references.citation: Genes Dev. 2012 Feb 1;26(3):203-34
references.pmid: 22302935
references.citation: Genome Res. 2011 Sep;21(9):1404-16
references.pmid: 21750107
references.citation: Genome Biol. 2009;10(3):R25
references.pmid: 19261174
references.citation: Nat Biotechnol. 2010 May;28(5):511-5
references.pmid: 20436464
references.citation: Nature. 2010 Jun 24;465(7301):1033-8
references.pmid: 20577206
references.citation: Nat Biotechnol. 2011 May 15;29(7):644-52
references.pmid: 21572440
references.citation: J Gerontol A Biol Sci Med Sci. 2011 Feb;66(2):191-201
references.pmid: 20974732
references.citation: J Invest Dermatol. 2013 Feb;133(2):394-402
references.pmid: 22931923
references.citation: Nat Genet. 2010 Dec;42(12):1113-7
references.pmid: 21057500
references.citation: Nature. 2012 Sep 6;489(7414):101-8
references.pmid: 22955620
references.citation: PLoS Genet. 2011 Jun;7(6):e1002153
references.pmid: 21738489
references.citation: Cell. 2012 Jun 22;149(7):1622-34
references.pmid: 22726445
references.citation: Mol Cell. 2011 Dec 9;44(5):785-96
references.pmid: 22152481
references.citation: Science. 2006 Jun 16;312(5780):1653-5
references.pmid: 16778056
references.citation: PLoS Biol. 2010 May 11;8(5):e1000384
references.pmid: 20485488
references.citation: PLoS Genet. 2009 Dec;5(12):e1000776
references.pmid: 20019809
references.citation: Neural Dev. 2011 Sep 21;6:32
references.pmid: 21936910
references.citation: Genes Dev. 2007 Dec 15;21(24):3244-57
references.pmid: 18055696
references.citation: Genome Res. 2006 Jan;16(1):11-9
references.pmid: 16344565
references.citation: Nature. 2011 Apr 7;472(7341):120-4
references.pmid: 21423168
references.citation: Curr Biol. 2010 Oct 12;20(19):R858-61
references.pmid: 20937476
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: Nat Genet. 2011 Jun 05;43(7):621-9
references.pmid: 21642992
references.citation: BMC Dev Biol. 2010 May 11;10:49
references.pmid: 20459797
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: RNA. 2009 Aug;15(8):1578-87
references.pmid: 19535462
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W345-9
references.pmid: 17631615
references.citation: Genome Biol. 2008;9(9):R137
references.pmid: 18798982
references.citation: Cell. 2011 Aug 5;146(3):353-8
references.pmid: 21802130
references.citation: Cell. 2011 May 13;145(4):622-34
references.pmid: 21549415
references.citation: Nat Biotechnol. 2010 May;28(5):503-10
references.pmid: 20436462
references.citation: Science. 2005 Sep 2;309(5740):1570-3
references.pmid: 16141075
references.citation: Science. 2010 Aug 6;329(5992):689-93
references.pmid: 20616235
references.citation: Sci Signal. 2010 Feb 02;3(107):ra8
references.pmid: 20124551
references.citation: Nature. 2009 Mar 12;458(7235):223-7
references.pmid: 19182780
references.citation: Stat Methods Med Res. 2013 Oct;22(5):519-36
references.pmid: 22127579
references.citation: Genes Dev. 2006 Jun 1;20(11):1470-84
references.pmid: 16705037
references.citation: Nat Neurosci. 2009 Aug;12(8):1020-7
references.pmid: 19620975