Mechanochemical Properties of Individual Human Telomeric RNA (TERRA) G‐Quadruplexes

Abstract

Potential functions: By following the unfolding and refolding of individual human RNA telomeric (TERRA) G-quadruplexes (GQs) in laser tweezers, the mechanical stability and transition kinetics of RNA GQs are obtained. Comparison between TERRA and DNA GQs suggests their different regulatory capacities for processes associated with human telomeres.

Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G‐Quadruplex

“…Using probability density distribution of Δ L and bootstrap statistical analyses (PoDNano,[ 23 ] see the Supporting Information), the Δ L histograms were deconvoluted into two major populations with Gaussian centers at 9.4±0.2 and 5.7±0.3 nm (Figure 1 B inset). Consistent with earlier reports,[ 24 ] these Δ L populations represent a GQ structure (9.4 nm) and partially folded species (5.7 nm). The latter may assume a G-Triplex[ 25 , 26 ] conformation.…”

“…The rupture-force histogram for the TERRA GQ without ligands shows more than one population (Figure 4 A ), representing multiple conformations in the same TERRA sequence as reported previously. [ 24 , 28 ] When the TERRA construct was incubated with 5 μ m cPDS, we observed an increase in the rupture forces (from 23/36 pN to 25/40 pN), thus suggesting that the binding of cPDS increases the mechanical stability of the TERRA GQ (Figure 4 B ). A similar increment in mechanical stability was observed for TERRA-G4 with 50 n m BG4 (Figure 4 C ).…”

Direct and Single‐Molecule Visualization of the Solution‐State Structures of G‐Hairpin and G‐Triplex Intermediates

“…Besides the investigations of the biological significance of G‐quadruplexes and therapeutic interests for cancer and AIDS, the studies on the folding pathway of G‐quadruplexes and the intermediate states involved are of ongoing interest. Only a few studies have been carried out on the folding pathway of quadruplexes and most of them were either based on theoretical calculations13–15 or assumptions derived from the experimental evidence 16–23. To date, very little is known on the intermediates and this is mainly due to the lack of techniques that can successfully isolate the intermediates.…”

Direct and Single‐Molecule Visualization of the Solution‐State Structures of G‐Hairpin and G‐Triplex Intermediates

“…Moreover, G-rich sequences have been shown to inhibit HIV type-1 replication in culture. [16][17][18][19][20][21][22][23] To date, very little is known on the intermediates and this is mainly due to the lack of techniques that can successfully isolate the intermediates. Only a few studies have been carried out on the folding pathway of quadruplexes and most of them were either based on theoretical calculations [13][14][15] or assumptions derived from the experimental evidence.…”

“…Only a few studies have been carried out on the folding pathway of quadruplexes and most of them were either based on theoretical calculations [13][14][15] or assumptions derived from the experimental evidence. [16][17][18][19][20][21][22][23] To date, very little is known on the intermediates and this is mainly due to the lack of techniques that can successfully isolate the intermediates. Based on the computational studies, we have recently proposed a folding pathway for the human telomeric Gquadruplexes (Figure 1 a) that progresses through intermediate states, such as G-hairpin (a G-G mismatched Hoogsteen duplex formed by two tandem guanine repeats) and G-triplex (a partly folded structure with three tandem guanine repeats bound together by Hoogsteen hydrogen bonding).…”