Long noncoding RNA NRON contributes to HIV-1 latency by specifically inducing tat protein degradation

Nat Commun. 2016 Jun 13;7:11730. doi: 10.1038/ncomms11730.

Abstract

Long noncoding RNAs (lncRNAs) play multiple key regulatory roles in various cellular pathways. However, their functions in HIV-1 latent infection remain largely unknown. Here we show that a lncRNA named NRON, which is highly expressed in resting CD4(+) T lymphocytes, could be involved in HIV-1 latency by specifically inducing Tat protein degradation. Our results suggest that NRON lncRNA potently suppresses the viral transcription by decreasing the cellular abundance of viral transactivator protein Tat. NRON directly links Tat to the ubiquitin/proteasome components including CUL4B and PSMD11, thus facilitating Tat degradation. Depletion of NRON, especially in combination with a histone deacetylase (HDAC) inhibitor, significantly reactivates the viral production from the HIV-1-latently infected primary CD4(+) T lymphocytes. Our data indicate that lncRNAs play a role in HIV-1 latency and their manipulation could be a novel approach for developing latency-reversing agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cullin Proteins / metabolism
  • HEK293 Cells
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Proteolysis*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transcription, Genetic
  • Ubiquitin / metabolism
  • Ubiquitination
  • Virus Latency / genetics*
  • Virus Replication / physiology
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • CUL4B protein, human
  • Cullin Proteins
  • NRON long noncoding RNA, human
  • RNA, Long Noncoding
  • Ubiquitin
  • tat Gene Products, Human Immunodeficiency Virus
  • PSMD11 protein, human
  • Proteasome Endopeptidase Complex