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Metal Cations in G-Quadruplex Folding and Stability

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ABSTRACT

This review is focused on the structural and physicochemical aspects of metal cation coordination to G-Quadruplexes (GQ) and their effects on GQ stability and conformation. G-quadruplex structures are non-canonical secondary structures formed by both DNA and RNA. G-quadruplexes regulate a wide range of important biochemical processes. Besides the sequence requirements, the coordination of monovalent cations in the GQ is essential for its formation and determines the stability and polymorphism of GQ structures. The nature, location, and dynamics of the cation coordination and their impact on the overall GQ stability are dependent on several factors such as the ionic radii, hydration energy, and the bonding strength to the O6 of guanines. The intracellular monovalent cation concentration and the localized ion concentrations determine the formation of GQs and can potentially dictate their regulatory roles. A wide range of biochemical and biophysical studies on an array of GQ enabling sequences have generated at a minimum the knowledge base that allows us to often predict the stability of GQs in the presence of the physiologically relevant metal ions, however, prediction of conformation of such GQs is still out of the realm.

No MeSH data available.


Structural switch in response to ionic environment in miRNA 92b may influence the processing and the biogenesis of the G-quadruplex harboring miRNAs.
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Figure 6: Structural switch in response to ionic environment in miRNA 92b may influence the processing and the biogenesis of the G-quadruplex harboring miRNAs.

Mentions: Switching or co-existence of hairpin and GQ structures has also been observed with RNA sequences. A designed RNA sequence which could either form a GQ structure or a hairpin but not simultaneously, formed GQ structure in presence of K+ ions, but in presence of Mg2+ converted to the hairpin structure (Bugaut et al., 2012). In a separate study our group showed that microRNA maturation from pre-microRNA was modulated by the equilibrium of the hairpin to GQ switch (Figure 6). Since the hairpin is an essential structural requirement for maturation, the population of the two structural variants in equilibrium dictates the amount of matured miRNA (Mirihana Arachchilage et al., 2015; Pandey et al., 2015). A very similar hairpin to GQ transition was observed in the DNA GQ forming sequence in WNT1 promoter. The hairpin transition to GQ was observed to be quite slow at 4800 s indicating that such switching may be a slow process (Kuo et al., 2015).


Metal Cations in G-Quadruplex Folding and Stability
Structural switch in response to ionic environment in miRNA 92b may influence the processing and the biogenesis of the G-quadruplex harboring miRNAs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5016522&req=5

Figure 6: Structural switch in response to ionic environment in miRNA 92b may influence the processing and the biogenesis of the G-quadruplex harboring miRNAs.
Mentions: Switching or co-existence of hairpin and GQ structures has also been observed with RNA sequences. A designed RNA sequence which could either form a GQ structure or a hairpin but not simultaneously, formed GQ structure in presence of K+ ions, but in presence of Mg2+ converted to the hairpin structure (Bugaut et al., 2012). In a separate study our group showed that microRNA maturation from pre-microRNA was modulated by the equilibrium of the hairpin to GQ switch (Figure 6). Since the hairpin is an essential structural requirement for maturation, the population of the two structural variants in equilibrium dictates the amount of matured miRNA (Mirihana Arachchilage et al., 2015; Pandey et al., 2015). A very similar hairpin to GQ transition was observed in the DNA GQ forming sequence in WNT1 promoter. The hairpin transition to GQ was observed to be quite slow at 4800 s indicating that such switching may be a slow process (Kuo et al., 2015).

View Article: PubMed Central - PubMed

ABSTRACT

This review is focused on the structural and physicochemical aspects of metal cation coordination to G-Quadruplexes (GQ) and their effects on GQ stability and conformation. G-quadruplex structures are non-canonical secondary structures formed by both DNA and RNA. G-quadruplexes regulate a wide range of important biochemical processes. Besides the sequence requirements, the coordination of monovalent cations in the GQ is essential for its formation and determines the stability and polymorphism of GQ structures. The nature, location, and dynamics of the cation coordination and their impact on the overall GQ stability are dependent on several factors such as the ionic radii, hydration energy, and the bonding strength to the O6 of guanines. The intracellular monovalent cation concentration and the localized ion concentrations determine the formation of GQs and can potentially dictate their regulatory roles. A wide range of biochemical and biophysical studies on an array of GQ enabling sequences have generated at a minimum the knowledge base that allows us to often predict the stability of GQs in the presence of the physiologically relevant metal ions, however, prediction of conformation of such GQs is still out of the realm.

No MeSH data available.