Loop permutation affects the topology and stability of G-quadruplexes

Area of Science:

• Molecular Biology
• Biophysics
• Genomics

Background:

• G-quadruplexes are crucial DNA and RNA secondary structures found across diverse organisms.
• Intramolecular G-quadruplex folding and stability are heavily influenced by loop regions.
• Previous research focused on loop length and composition, neglecting loop permutation's impact.

Purpose of the Study:

• To systematically investigate the effect of loop permutation on G-quadruplex conformation and thermal stability.
• To compare the significance of loop permutation against loop length and base composition.
• To identify potential regulatory roles and therapeutic targets of G-quadruplexes in genomes.

Main Methods:

• Tested 99 G-quadruplex sequences across 21 groups with varying loop permutations.
• Analyzed changes in G-quadruplex conformation and thermal stability (Tm).
• Cross-referenced sequences with genomic databases of diverse organisms.

Main Results:

• Loop permutation significantly alters G-quadruplex conformation and thermal stability, with Tm shifts up to 17°C.
• Longer central loops favor stable non-parallel topologies, while shorter ones lead to less stable parallel topologies.
• Over 50% of tested sequences were identified in various organism genomes, suggesting biological relevance.

Conclusions:

• Loop permutation is a critical determinant of G-quadruplex folding, comparable in importance to loop length and base composition.
• Findings provide insights into G-quadruplex structural dynamics and can aid in predicting folding patterns and stability.
• The prevalence of these sequences in genomes highlights their potential functional and therapeutic significance.