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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Phenomena
  • Chromatin / metabolism
  • Cytokines / metabolism
  • Feedback
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • Humans
  • Immunity, Innate / drug effects
  • Interferons / metabolism*
  • Lipopolysaccharides / adverse effects
  • Mice
  • Myeloid Cells / metabolism
  • Oxidoreductases Acting on CH-CH Group Donors
  • Proteins
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • STAT1 Transcription Factor / metabolism
  • THP-1 Cells

Substances

  • Chromatin
  • Cytokines
  • Lipopolysaccharides
  • MALAT1 long non-coding RNA, human
  • Proteins
  • RNA, Long Noncoding
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • long non-coding RNA LUCAT1, human
  • Interferons
  • Oxidoreductases Acting on CH-CH Group Donors
  • RSAD2 protein, human