Monomorphic RNA G-quadruplex and polymorphic DNA G-quadruplex structures responding to cellular environmental factors

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• G-quadruplexes are four-stranded nucleic acid structures formed in guanine-rich regions.
• Understanding G-quadruplex formation and stability is crucial for various biological processes.
• Molecular crowding conditions in cells significantly impact biomolecular structures and functions.

Purpose of the Study:

• To investigate the structure and thermodynamics of RNA and DNA G-quadruplexes under molecular crowding.
• To compare the stability and structural characteristics of RNA G-quadruplexes versus DNA G-quadruplexes.
• To elucidate the role of water molecules in RNA G-quadruplex formation and stability.

Main Methods:

• Systematic and quantitative investigation of G-quadruplex structures.
• Thermodynamic analysis under dilute and molecular crowding conditions.
• Structural analysis of telomere RNA and DNA sequences, including a human bcl-2 mRNA sequence.

Main Results:

• RNA G-quadruplexes consistently formed stable, parallel structures across tested conditions.
• DNA G-quadruplexes exhibited structural polymorphism.
• RNA G-quadruplexes were found to be significantly more stable than their corresponding DNA counterparts.
• A specific bcl-2 mRNA G-quadruplex demonstrated high stability under all tested conditions.

Conclusions:

• A single, robust RNA G-quadruplex structure can form independently of sequence and surrounding conditions.
• RNA G-quadruplexes offer greater stability compared to DNA G-quadruplexes.
• Water molecule interactions with the 2'-OH group are critical for RNA G-quadruplex stability.