Study of G-quadruplexes in the STAT3 gene using electrospray ionization mass spectrometry

Abstract

RATIONALE: As a key signal transducer and transcription activator, STAT3 plays a very important role in many cell processes. We found that there were many G-rich sequences existing in the STAT3 gene including its promoter, intron, exon and 3′-flanking regions. These G-rich tracts can form G-quadruplexes under near physiological conditions. In this research, we systemically studied the G-quadruplexes in the STAT3 gene at a whole gene scale for the first time. METHODS: In this research, the formation of G-quadruplexes in the STAT3 gene was probed by electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD). Their structures were constructed and refined by a molecular modeling method. We also used ESI-MS to study the recognition of the G-quadruplexes in the promoter of the STAT3 gene by flexible molecules which do not have a planar core like the other common quadruplex ligands. RESULTS: The results based on ESI-MS suggested that the G-quadruplexes in the promoter of the STAT3 gene formed and were further recognized by some small molecules. CONCLUSION: Our research proved that the G-rich sequences in the STAT3 gene could form G-quadruplexes under near physiological conditions. This provides a promising target to study the regulation of cell signal transduction in vivo and drug design that aims to target STAT3 G-quadruplexes.