title: Probing the G‑quadruplex from hsa-miR-3620-5p and inhibition of its interaction with the target sequence.
abstract: G-quadruplexes have been reported to exist both in human genome and transcriptome and are of great interests due to their important biological functions. Up to now, the formation and property of G-quadruplex in human mature microRNAs has not been explored yet. In this study, we discovered that hsa-miR-3620-5p, a guanine rich human mature microRNA, could fold into a stable parallel G-quadruplex in near physiological condition for the first time. We explored the formation, folding pattern and binding affinity of the miR-3620-5p G-quadruplex by ESI-MS, CD, NMR and SPR. The results indicated that its high-order structure was comprised of three G-quartets with two bases in each parallel loop stretching outward and two bases flanking at each end. In addition, sanguinarine, a natural alkaloid screened from traditional Chinese medicine was characterized to have high binding affinity and thermodynamic stabilization effects through π-π stacking interaction with the external G-quartets. Furthermore, the potent interaction of sanguinarine with miR-3620-5p G-quadruplex could block the base pairing between miR-3620-5p and its target sequence. Therefore, our study revealed the possibility of regulating microRNA functions using potent G-quadruplex binders, and could provide a new approach to affect the microRNA:mRNA interactions.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: zhoujiang@pku.edu.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Jiangyong
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: guyuan@pku.edu.cn.
authors.forename: Gu
authors.initials: G
authors.lastname: Yuan
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D054856:G-Quadruplexes; D006801:Humans; D035683:MicroRNAs; D012333:RNA, Messenger; D013816:Thermodynamics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: ESI-MS; Folding pattern; G-quadruplex; MicroRNA; Natural alkaloid