linc-AAM Facilitates Gene Expression Contributing to Macrophage Activation and Adaptive Immune Responses

Cell Rep. 2021 Jan 5;34(1):108584. doi: 10.1016/j.celrep.2020.108584.

Abstract

Although various long noncoding RNAs (lncRNAs) are specifically expressed in activated macrophages, their in vivo functions and mechanisms of action are largely unexplored. Here, we identify a long intergenic noncoding RNA associated with activated macrophage (linc-AAM) and elucidate its function and mechanisms. linc-AAM is highly expressed in activated macrophages. In vitro function analysis reveals that linc-AAM facilitates macrophage activation and promotes the expression of immune response genes (IRGs). In mechanisms, linc-AAM interacts with heterogeneous nuclear ribonucleoprotein L (hnRNPL) via two CACACA motifs, resulting in its dissociation from histone H3 to activate chromatin and facilitate transcription of IRGs. Of note, linc-AAM knockout (KO) mice manifest impaired antigen-specific cellular and humoral immune responses to ovalbumin (OVA) in vivo. Altogether, the results uncover a mechanism of lncRNA in modulating hnRNPL function and confirm that linc-AAM acts as a transcription enhancer to activate macrophages and promote adaptive immunity.

Keywords: adaptive immune response; hnRNPL; immune response gene; linc-AAM; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Cell Line
  • Cells, Cultured
  • Chromatin / metabolism
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • Heterogeneous-Nuclear Ribonucleoprotein L / physiology*
  • Histones / metabolism
  • Humans
  • Immunity, Humoral
  • Macrophage Activation*
  • Macrophages / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Interaction Domains and Motifs
  • RNA, Long Noncoding / physiology*

Substances

  • Chromatin
  • Heterogeneous-Nuclear Ribonucleoprotein L
  • Histones
  • RNA, Long Noncoding