The Long Noncoding RNA NEAT1 and Nuclear Paraspeckles Are Up-Regulated by the Transcription Factor HSF1 in the Heat Shock Response

J Biol Chem. 2018 Dec 7;293(49):18965-18976. doi: 10.1074/jbc.RA118.004473. Epub 2018 Oct 10.

Abstract

The long noncoding RNA (lncRNA) NEAT1 (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. NEAT1 and paraspeckle formation are increased in cells upon exposure to a variety of environmental stressors and believed to play an important role in cell survival. The present study was undertaken to further investigate the role of NEAT1 in cellular stress response pathways. We show that NEAT1 is a novel target gene of heat shock transcription factor 1 (HSF1) and is up-regulated when the heat shock response pathway is activated by sulforaphane (SFN) or elevated temperature. HSF1 binds specifically to a newly identified conserved heat shock element in the NEAT1 promoter. In line with this, SFN induced the formation of NEAT1-containing paraspeckles via an HSF1-dependent mechanism. HSF1 plays a key role in the cellular response to proteotoxic stress by promoting the expression of a series of genes, including those encoding molecular chaperones. We have found that the expression of HSP70, HSP90, and HSP27 is amplified and sustained during heat shock in NEAT1-depleted cells compared with control cells, indicating that NEAT1 feeds back via an unknown mechanism to regulate HSF1 activity. This interrelationship is potentially significant in human diseases such as cancer and neurodegenerative disorders.

Keywords: NEAT1; gene expression; heat shock factor protein 1 (HSF1); heat shock protein (HSP); heat shock response; long noncoding RNA (long ncRNA, lncRNA); paraspeckle; sulforaphane; transcription regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Nucleus Structures / metabolism*
  • Cell Proliferation
  • HSP27 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Heat Shock Transcription Factors / metabolism*
  • Heat-Shock Response / genetics
  • Heat-Shock Response / physiology*
  • Humans
  • Isothiocyanates / pharmacology
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Up-Regulation

Substances

  • HSF1 protein, human
  • HSP27 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat Shock Transcription Factors
  • Isothiocyanates
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Ribonucleoproteins
  • sulforafan