Title
Unexpected Position-dependent Effects of Ribose G-quartets in G-quadruplexes
Author
Jun Zhou, Samir Amrane, Frédéric Rosu, Gilmar F. Salgado, Yunqiang Bian, Hisae Tateishi-Karimata, Eric Largy, Dursun Nizam Korkut, Anne Bourdoncle, Daisuke Miyoshi, Jian Zhang, Huangxian Ju, Wei Wang, Naoki Sugimoto, Valérie Gabelica, Jean-Louis Mergny
Year
2017
Journal
JACS
Abstract
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 present 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 (lower case 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.
Full Article
Instrument
J-815
Keywords
Circular dichroism, DNA structure, RNA structure, Thermal stability, Thermodynamics, Biochemistry