Long noncoding RNA #32 contributes to antiviral responses by controlling interferon-stimulated gene expression

Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):10388-93. doi: 10.1073/pnas.1525022113. Epub 2016 Aug 31.

Abstract

Despite the breadth of knowledge that exists regarding the function of long noncoding RNAs (lncRNAs) in biological phenomena, the role of lncRNAs in host antiviral responses is poorly understood. Here, we report that lncRNA#32 is associated with type I IFN signaling. The silencing of lncRNA#32 dramatically reduced the level of IFN-stimulated gene (ISG) expression, resulting in sensitivity to encephalomyocarditis virus (EMCV) infection. In contrast, the ectopic expression of lncRNA#32 significantly suppressed EMCV replication, suggesting that lncRNA#32 positively regulates the host antiviral response. We further demonstrated the suppressive function of lncRNA#32 in hepatitis B virus and hepatitis C virus infection. lncRNA#32 bound to activating transcription factor 2 (ATF2) and regulated ISG expression. Our results reveal a role for lncRNA#32 in host antiviral responses.

Keywords: ISG; innate immunity; interferon; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / genetics*
  • Activating Transcription Factor 2 / metabolism
  • Cardiovirus Infections / genetics
  • Cardiovirus Infections / virology
  • Cell Line, Tumor
  • Encephalomyocarditis virus / genetics
  • Encephalomyocarditis virus / pathogenicity
  • Gene Expression Regulation
  • Gene Silencing
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatitis C / genetics
  • Hepatitis C / virology
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Interferon Type I / genetics*
  • Interferon Type I / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction / genetics
  • Virus Replication / genetics

Substances

  • ATF2 protein, human
  • Activating Transcription Factor 2
  • Interferon Type I
  • RNA, Long Noncoding