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The genomic sequences near the mir‐23b‐27b‐24‐1 cluster form G‐quadruplexes and are selectively bound by the natural alkaloid tetrandrine
Author(s) -
Qi Yanchao,
Chen Han,
Tan Wei,
Li Yanyan,
Yuan Gu,
Xu Ming
Publication year - 2015
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7251
Subject(s) - tetrandrine , chemistry , g quadruplex , antiparallel (mathematics) , circular dichroism , electrospray ionization , stereochemistry , cluster (spacecraft) , mass spectrometry , crystallography , biochemistry , chromatography , dna , biology , physics , quantum mechanics , magnetic field , computer science , pharmacology , programming language
Rationale Although the microRNAs miR‐23b, miR‐27b and miR‐24 are located in the same cluster, their expressions in various pathological states are not always comparable. By searching the genomic sequence around mir23b‐27b‐24‐1 in rat, we identified three potential G‐quadruplex sequences (PQS) which can fold into different types of G‐quadruplexes, including parallel or antiparallel. Natural alkaloids, tetrandrine (TET), displayed different binding affinity with the three G‐quadruplexes which may potentially regulate the expression of mir23b‐27b‐24‐1 cluster members. Methods Both electrospray ionization mass spectrometry (ESI‐MS) and circular dichroism (CD) spectroscopy were utilized to detect the formation of G‐quadruplexes. Six small molecules were screened by ESI‐MS for their binding affinity with three G‐quadruplexes, which were evaluated by their IR a values. Results The results of ESI‐MS and CD experiments confirmed the formation of three G‐quadruplexes neighboring the mir23b‐27b‐24‐1 cluster; two of them adopted antiparallel G‐quadruplexes, another adopted a parallel G‐quadruplex. Screening of small molecules by ESI‐MS showed tetrandrine had selective binding affinity for the parallel G‐quadruplex. G‐quadruplex stabilization by tetrandrine was verified by CD variable temperature measurements. Conclusions The gene of the mir23b‐27b‐24‐1 cluster harbors three G‐quadruplexes with typical sequences and structures. Tetrandrine had a selective binding affinity to the parallel G‐quadruplex and stabilized it significantly. Copyright © 2015 John Wiley & Sons, Ltd.