title: The formation and stabilization of a novel G-quadruplex in the 5'-flanking region of the relaxin gene.
abstract: It has been reported that binding of STAT3 protein to the 5'-flanking region of the relaxin gene may result in downregulation of the relaxin expression. There is a Guanine(G)-rich segment located in about 3.8 Kb upstream of the relaxin gene and very close to the STAT3's binding site. In our study, NMR spectroscopy revealed the formation of G-quadruplex by this G-rich strand, and the result was confirmed by ESI mass spectrometry and CD spectroscopy. The theoretical structure of RLX G-quadruplex was constructed and refined by molecular modeling. When this relaxin G-quadruplex was stabilized by berberine(ΔTm = 10°C), a natural alkaloid from a Chinese herb, the gene expression could be up-regulated in a dose-dependent manner which was proved by luciferase assay. This result is different from the general G-quadruplex function that inhibiting the telomere replication or down-regulating many oncogenes expression. Therefore, our study reported a novel G-quadruplex in the relaxin gene and complemented the regulation mechanism about gene expression by G-quadruplexes.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Lin
authors.forename: Huiping
authors.initials: H
authors.lastname: Gu
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Cui
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Gu
authors.initials: G
authors.lastname: Yuan
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001599:Berberine / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D057075:Enzyme Assays; D054856:G-Quadruplexes; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051381:Rats; D012065:Relaxin / Q000235:genetics*; D044366:Transition Temperature; D015854:Up-Regulation / Q000235:genetics
chemical_list: D001599:Berberine; D012065:Relaxin; D008156:Luciferases