A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress

Nucleic Acids Res. 2013 Feb 1;41(3):1533-43. doi: 10.1093/nar/gks1232. Epub 2012 Dec 14.

Abstract

We reported that non-targeting siRNA (NT-siRNA) stress induces non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) expression to cooperate with exoribonuclease XRN2 for releasing the stress [Wei,P.C., Lo,W.T., Su,M.I., Shew,J.Y. and Lee,W.H. (2011) Non-targeting siRNA induces NPGPx expression to cooperate with exoribonuclease XRN2 for releasing the stress. Nucleic Acids Res., 40, 323-332]. However, how NT-siRNA stress inducing NPGPx expression remains elusive. In this communication, we showed that the proximal promoter of NPGPx contained a mixed G-quadruplex (G4) structure, and disrupting the structure diminished NT-siRNA induced NPGPx promoter activity. We also demonstrated that nucleolin (NCL) specifically bonded to the G4-containing sequences to replace the originally bound Sp1 at the NPGPx promoter on NT-siRNA stress. Consistently, overexpression of NCL further increased NPGPx promoter activity, whereas depletion of NCL desensitized NPGPx promoter to NT-siRNA stress. These results suggest that the cis-element with mixed G4 structure at the NPGPx promoter plays an essential role for its transactivation mediated by NCL to release cells from NT-siRNA stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • G-Quadruplexes*
  • GC Rich Sequence
  • Humans
  • Peroxidases / genetics*
  • Peroxidases / metabolism
  • Phosphoproteins / metabolism*
  • Promoter Regions, Genetic*
  • RNA, Small Interfering*
  • RNA-Binding Proteins / metabolism*
  • Sp1 Transcription Factor / metabolism
  • Stress, Physiological / genetics*
  • Transcriptional Activation*
  • Up-Regulation

Substances

  • Phosphoproteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Sp1 Transcription Factor
  • nucleolin
  • Peroxidases