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

Author

Listed:
  • 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

    (UniversiteĢ de Lyon, ENSL, UCBL, CNRS, INSERM, LBMC)

  • Katherine A. Fitzgerald

    (University of Massachusetts Medical School)

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.

Suggested Citation

  • Shiuli Agarwal & Tim Vierbuchen & Sreya Ghosh & Jennie Chan & Zhaozhao Jiang & Richard K. Kandasamy & Emiliano Ricci & Katherine A. Fitzgerald, 2020. "The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20165-5
    DOI: 10.1038/s41467-020-20165-5
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    Cited by:

    1. Amir Argoetti & Dor Shalev & Galia Polyak & Noa Shima & Hadas Biran & Tamar Lahav & Tamar Hashimshony & Yael Mandel-Gutfreund, 2025. "lncRNA NORAD modulates STAT3/STAT1 balance and innate immune responses in human cells via interaction with STAT3," Nature Communications, Nature, vol. 16(1), pages 1-14, December.

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