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dc.contributor.authorVierbuchen, Tim
dc.contributor.authorAgarwal, Shiuli
dc.contributor.authorJohnson, John L
dc.contributor.authorGalia, Liraz
dc.contributor.authorLei, Xuqiu
dc.contributor.authorStein, Karina
dc.contributor.authorOlagnier, David
dc.contributor.authorGaede, Karoline I
dc.contributor.authorHerzmann, Christian
dc.contributor.authorHolm, Christian K
dc.contributor.authorHeine, Holger
dc.contributor.authorPai, Athma
dc.contributor.authorO'Hara Hall, Aisling
dc.contributor.authorHoebe, Kasper
dc.contributor.authorFitzgerald, Katherine A
dc.date.accessioned2024-04-26T20:15:20Z
dc.date.available2024-04-26T20:15:20Z
dc.date.issued2022-12-28
dc.identifier.citationVierbuchen T, Agarwal S, Johnson JL, Galia L, Lei X, Stein K, Olagnier D, Gaede KI, Herzmann C, Holm CK, Heine H, Pai A, O'Hara Hall A, Hoebe K, Fitzgerald KA. The lncRNA LUCAT1 is elevated in inflammatory disease and restrains inflammation by regulating the splicing and stability of NR4A2. Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2213715120. doi: 10.1073/pnas.2213715120. Epub 2022 Dec 28. PMID: 36577072; PMCID: PMC9910463.en_US
dc.identifier.eissn1091-6490
dc.identifier.doi10.1073/pnas.2213715120en_US
dc.identifier.pmid36577072
dc.identifier.urihttp://hdl.handle.net/20.500.14038/53319
dc.description.abstractThe nuclear long non-coding RNA LUCAT1 has previously been identified as a negative feedback regulator of type I interferon and inflammatory cytokine expression in human myeloid cells. Here, we define the mechanistic basis for the suppression of inflammatory gene expression by LUCAT1. Using comprehensive identification of RNA-binding proteins by mass spectrometry as well as RNA immunoprecipitation, we identified proteins important in processing and alternative splicing of mRNAs as LUCAT1-binding proteins. These included heterogeneous nuclear ribonucleoprotein C, M, and A2B1. Consistent with this finding, cells lacking LUCAT1 have altered splicing of selected immune genes. In particular, upon lipopolysaccharide stimulation, the splicing of the nuclear receptor 4A2 (NR4A2) gene was particularly affected. As a consequence, expression of NR4A2 was reduced and delayed in cells lacking LUCAT1. NR4A2-deficient cells had elevated expression of immune genes. These observations suggest that LUCAT1 is induced to control the splicing and stability of NR4A2, which is in part responsible for the anti-inflammatory effect of LUCAT1. Furthermore, we analyzed a large cohort of patients with inflammatory bowel disease as well as asthma and chronic obstructive pulmonary disease. In these patients, LUCAT1 levels were elevated and in both diseases, positively correlated with disease severity. Collectively, these studies define a key molecular mechanism of LUCAT1-dependent immune regulation through post-transcriptional regulation of mRNAs highlighting its role in the regulation of inflammatory disease.en_US
dc.language.isoenen_US
dc.relation.ispartofProceedings of the National Academy of Sciencesen_US
dc.relation.urlhttps://doi.org/10.1073/pnas.2213715120en_US
dc.rightsCopyright © 2022 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectinterferonen_US
dc.subjectlncRNAen_US
dc.subjectsplicingen_US
dc.titleThe lncRNA LUCAT1 is elevated in inflammatory disease and restrains inflammation by regulating the splicing and stability of NR4A2en_US
dc.typeJournal Articleen_US
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume120
dc.source.issue1
dc.source.beginpagee2213715120
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of America
refterms.dateFOA2024-04-26T20:15:21Z
dc.contributor.departmentMedicineen_US
dc.contributor.departmentRNA Therapeutics Instituteen_US


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Copyright © 2022 the Author(s). Published by PNAS.
This article is distributed under Creative Commons
Attribution-NonCommercial-NoDerivatives License 4.0
(CC BY-NC-ND).
Except where otherwise noted, this item's license is described as Copyright © 2022 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).