The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans

Shiuli Agarwal, Tim Vierbuchen, Sreya Ghosh, Jennie Chan, Zhaozhao Jiang, Richard K. Kandasamy, Emiliano Ricci and Katherine A. Fitzgerald ()
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Shiuli Agarwal: University of Massachusetts Medical School
Tim Vierbuchen: University of Massachusetts Medical School
Sreya Ghosh: University of Massachusetts Medical School
Jennie Chan: University of Massachusetts Medical School
Zhaozhao Jiang: University of Massachusetts Medical School
Richard K. Kandasamy: Norwegian University of Science and Technology
Emiliano Ricci: Université de Lyon, ENSL, UCBL, CNRS, INSERM, LBMC
Katherine A. Fitzgerald: University of Massachusetts Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20165-5

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