title: The kinetics and folding pathways of intramolecular G-quadruplex nucleic acids.
abstract: The folding kinetics of G-quadruplex forming sequences is critical to their capacity to influence biological function. While G-quadruplex structure and stability have been relatively well studied, little is known about the kinetics of their folding. We employed a stopped-flow mixing technique to systematically investigate the potassium-dependent folding kinetics of telomeric RNA and DNA G-quadruplexes and RNA G-quadruplexes containing only two G-quartets formed from sequences r[(GGA)(3)GG] and r[(GGUUA)(3)GG]. Our findings suggest a folding mechanism that involves two kinetic steps with initial binding of a single K(+), irrespective of the number of G-quartets involved or whether the G-quadruplex is formed from RNA or DNA. The folding rates for telomeric RNA and DNA G-quadruplexes are comparable at near physiological [K(+)] (90 mM) (τ = ~60 ms). The folding of a 2-quartet RNA G-quadruplex with single nucleotide A loops is considerably slower (τ = ~700 ms), and we found that the time required to fold a UUA looped variant (τ > 100 s, 500 mM K(+)) exceeds the lifetimes of some regulatory RNAs. We discuss the implications of these findings with respect to the fundamental properties of G-quadruplexes and their potential functions in biology.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge CB2 1EW, United Kingdom.
authors.forename: Amy Y Q
authors.initials: AY
authors.lastname: Zhang
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
mesh_terms: D002942:Circular Dichroism; D054856:G-Quadruplexes; D007700:Kinetics; D017510:Protein Folding