title: A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress.
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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, 11490 Taipei, Taiwan.
authors.forename: Pei-Chi
authors.initials: PC
authors.lastname: Wei
authors.forename: Zi-Fu
authors.initials: ZF
authors.lastname: Wang
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Lo
authors.forename: Mei-I
authors.initials: MI
authors.lastname: Su
authors.forename: Jin-Yuh
authors.initials: JY
authors.lastname: Shew
authors.forename: Ta-Chau
authors.initials: TC
authors.lastname: Chang
authors.forename: Wen-Hwa
authors.initials: WH
authors.lastname: Lee
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D054856:G-Quadruplexes; D020862:GC Rich Sequence; D006801:Humans; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D015533:Transcriptional Activation; D015854:Up-Regulation; D000097796:Nucleolin
chemical_list: D010544:Peroxidases; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016329:Sp1 Transcription Factor; D000097796:Nucleolin