Unexpected Position-Dependent Effects of Ribose G-Quartets in G-Quadruplexes

Journal of the American Chemical Society

5 years ago

Unexpected Position-Dependent Effects of Ribose G-Quartets in G-Quadruplexes

Huangxian Ju, Daisuke Miyoshi, Samir Amrane, Wei Wang, Yunqiang Bian, Dursun Nizam Korkut, Gilmar F. Salgado, Jian Zhang, Naoki Sugimoto, Hisae Tateishi-Karimata, Jun Zhou, Jean-Louis Mergny, Anne Bourdoncle, Valérie Gabelica, Eric Largy, Frédéric Rosu

To understand the role of ribose G-quartets and how they affect the properties of G-quadruplex structures, we studied three systems in which one, two, three, or four deoxyribose G-quartets were substituted with ribose G-quartets. These systems were a parallel DNA intramolecular G-quadruplex, d(TTGGGTGGGTTGGGTGGGTT), and two tetramolecular G-quadruplexes, d(TGGGT) and d(TGGGGT). Thermal denaturation experiments revealed that ribose G-quartets have position-dependent and cumulative effects on G-quadruplex stability. An unexpected destabilization was observed when rG quartets were presented at the 5′-end of the G stack. This observation challenges the general belief that RNA residues stabilize G-quadruplexes. Furthermore, in contrast to past proposals, hydration is not the main factor determining the stability of our RNA/DNA chimeric G-quadruplexes. Interestingly, the presence of rG residues in a central G-quartet facilitated the formation of additional tetramolecular G-quadruplex topologies showing positive circular dichroism signals at 295 nm. 2D NMR analysis of the tetramolecular TGgGGT (lowercase letter indicates ribose) indicates that Gs in the 5′-most G-quartet adopt the syn conformation. These analyses highlight several new aspects of the role of ribose G-quartets on G-quadruplex structure and stability, and demonstrate that the positions of ribose residues are critical for tuning G-quadruplex properties.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b00648

DOI: 10.1021/jacs.7b00648