The diverse structural landscape of quadruplexes

G-quadruplexes are secondary structures formed in G-rich sequences in DNA and RNA. Considerable research over the past three decades has led to in-depth insight into these unusual structures in DNA. Since the more recent exploration into RNA G-quadruplexes, such structures have demonstrated their in cellulo existence, function and roles in pathology. In comparison to Watson-Crick-based secondary structures, most G-quadruplexes display highly redundant structural characteristics. However, numerous reports of G-quadruplex motifs/structures with unique features (e.g. bulges, long loops, vacancy) have recently surfaced, expanding the repertoire of G-quadruplex scaffolds. This review addresses G-quadruplex formation and structure, including recent reports of non-canonical G-quadruplex structures. Improved methods of detection will likely further expand this collection of novel structures and ultimately change the face of quadruplex-RNA targeting as a therapeutic strategy.