Deciphering the intermolecular interactions between G-quadruplex (G4)-forming sequences

Interactions between biomolecules govern cellular biology. While protein/protein and protein/nucleic acid (DNA, RNA) interactions—and, to a lesser extent, RNA/RNA and RNA/DNA interactions—have been extensively described, a question remains as to whether and how non-canonical DNA structures might interact with each other. This is of particular interest for guanine (G)-rich sequences that can fold into G-quadruplex (G4) structures: Individual G4s are currently studied for their involvement in a myriad of cellular events (mostly pertaining to the control of gene expression), and, more recently, the interactions between two G4s have been scrutinized as being part of a novel gene expression regulatory mechanism involving chromatin remodeling through G4-mediated loop formation. The question that needs to be answered is whether G4s or their corresponding G-rich sequences are involved. We present here a series of results collected using a combination of sequences, experimental conditions, and techniques, which led us to the conclusion that G4/G4 intermolecular interactions are mostly governed by primary sequence interactions in vitro.