Quadruplexes

G-quadruplexes (G4) are intricate, non-canonical nucleic acid structures in guanine-rich sequences. In general, four guanines are arranged in a cyclic plane, and two to four such planes are stacked to form a G-quadruplex core. These structures are universally present in all domains of life, including the human genome. The G4 has been shown to regulate gene replication and protein expression. Therefore, G4s are considered a promising target for chemotherapy. Several small molecules have been designed as specific G4 binders to interfere with their normal function in vivo. To date, most studies have focused on DNA G4s, while the understanding of RNA G4s is far from complete.

In our group, we are investigating the structural and dynamic properties of RNA G4s using NMR and biochemical assays, as well as the influence of small molecule interactions. Currently, we are investigating the BCL2 RNA G4. Our goal is to elucidate the causes of this highly dynamic system and to find ways to use the knowledge we gain to target downstream protein expression.

Qian Cao, Yi Li, Eva Freisinger, Peter Z. Qin*, Roland K. O. Sigel*, Zong-Wan Mao*, Inorg. Chem. Front., 2017, 4, 10-32.
doi:10.1039/C6QI00300A

Helena Guiset Miserachs, Daniela Donghi, Richard Börner*, Silke Johannsen*, Roland K. O. Sigel*, J. Biol. Inorg. Chem., 2016, 21, 975-986.
doi:10.1007/s00775-016-1393-4

Sebastian L.B. König, Julian L. Huppert, Roland K.O. Sigel RKO, Amanda C. Evans*, Nucleic Acid Res., 2013, 41(15), 7453–7461.
doi:10.1093/nar/gkt476