The NF-κB-Responsive Long Noncoding RNA FIRRE Regulates Posttranscriptional Regulation of Inflammatory Gene Expression through Interacting with hnRNPU

J Immunol. 2017 Nov 15;199(10):3571-3582. doi: 10.4049/jimmunol.1700091. Epub 2017 Oct 9.

Abstract

Long noncoding RNAs, a newly identified class of noncoding RNAs, are important regulators of gene expression in innate immunity. We report in this study that the transcription of FIRRE, a conserved long noncoding RNA between humans and mice, is controlled by NF-κB signaling in macrophages and intestinal epithelial cells. Functionally, FIRRE appears to positively regulate the expression of several inflammatory genes in macrophages or intestinal epithelial cells in response to LPS stimulation via posttranscriptional mechanisms. Specifically, FIRRE physically interacts with heterogeneous nuclear ribonucleoproteins U, regulating the stability of mRNAs of selected inflammatory genes through targeting the AU-rich elements of their mRNAs in cells following LPS stimulation. Therefore, our data indicate a new regulatory role for NF-κB-responsive FIRRE in the posttranscriptional regulation of inflammatory genes in the innate immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conserved Sequence / genetics*
  • Gene Expression Regulation
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • Immunity, Innate
  • Inflammation / genetics*
  • Intestinal Mucosa / immunology*
  • Macrophages / immunology*
  • Mice
  • NF-kappa B / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • Response Elements / genetics*
  • U937 Cells

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • NF-kappa B
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • long noncoding RNA Firre, human