UMMS Affiliation

Program in Innate Immunity; Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2020-12-11

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Hemic and Immune Systems | Immunology and Infectious Disease | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

Long non-coding RNAs are important regulators of biological processes including immune responses. The immunoregulatory functions of lncRNAs have been revealed primarily in murine models with limited understanding of lncRNAs in human immune responses. Here, we identify lncRNA LUCAT1 which is upregulated in human myeloid cells stimulated with lipopolysaccharide and other innate immune stimuli. Targeted deletion of LUCAT1 in myeloid cells increases expression of type I interferon stimulated genes in response to LPS. By contrast, increased LUCAT1 expression results in a reduction of the inducible ISG response. In activated cells, LUCAT1 is enriched in the nucleus where it associates with chromatin. Further, LUCAT1 limits transcription of interferon stimulated genes by interacting with STAT1 in the nucleus. Together, our study highlights the role of the lncRNA LUCAT1 as a post-induction feedback regulator which functions to restrain the immune response in human cells.

Keywords

Immunology, Innate immunity

Rights and Permissions

Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-020-20165-5

Source

Agarwal S, Vierbuchen T, Ghosh S, Chan J, Jiang Z, Kandasamy RK, Ricci E, Fitzgerald KA. The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans. Nat Commun. 2020 Dec 11;11(1):6348. doi: 10.1038/s41467-020-20165-5. PMID: 33311506; PMCID: PMC7733444. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Related Resources

Link to Article in PubMed

PubMed ID

33311506

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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