Overview of the RNA G-quadruplex structures

G-quadruplexes are non-canonical secondary structures which may be formed by guanine rich sequences, both in vitro and in living cells. The number of biological functions assigned to these structural motifs has grown rapidly since the discovery of their involvement in the telomere maintenance. Knowledge of the G-quadruplexes' three-dimensional structures plays an important role in understanding of their conformational diversity, physiological functions, and in the design of novel drugs targeting the G-quadruplexes. In the last decades, structural studies have been mainly focused on the DNA G-quadruplexes. Their RNA counterparts gained an increased interest along with a still-emerging recognition of the central role of RNA in multiple cellular processes. In this review we focus on structural properties of the RNA G-quadruplexes, based on high-resolution structures available in the RCSB PDB data base and on structural models. In addition, we point out the current challenges in this field of research

Distinctive structural motifs of RNA G-quadruplexes composed of AGG, CGG and UGG trinucleotide repeats

International audienceTrinucleotide repeats are microsatellite sequences that are polymorphic in length. Their expansion in specific genes underlies a number of neurode-generative disorders. Using ultraviolet-visible, circular dichroism, nuclear magnetic resonance (NMR) spectroscopies and electrospray ionization mass spectrometry, the structural preferences of RNA molecules composed of two and four repeats of AGG, CGG and UGG in the presence of K + , Na + and NH 4 + were analysed. (AGG) 2 A, (AGG) 4 A, p(UGG) 2 U and p(UGG) 4 U strongly prefer folding into G-quadruplexes, whereas CGG-containing sequences can adopt different types of structure depending on the cation and on the number of repeats. In particular, the two-repeat CGG sequence folds into a G-quadruplex in potassium buffer. We also found that each G-quadruplex fold is different: A:(G:G:G:G)A hexads were found for (AGG) 2 A, whereas mixed G:C:G:C tetrads and U-tetrads were observed in the NMR spectra of G(CGG) 2 C and p(UGG) 2 U, respectively. Finally, our NMR study highlights the influence of the strand sequence on the structure formed, and the influence of the intracellu-lar environment on the folding. Importantly, we highlight that although potassium ions are prevalent in cells, the structures observed in the HeLa cell extract are not always the same as those prevailing in biophysical studies in the presence of K + ions