Sequence Determinants of G-Quadruplex Thermostability: Aligning Evidence from High-Precision Biophysics and...

Area of Science:

• Molecular Biology
• Biophysics
• Genomics

Background:

• G-quadruplexes (G4s) are non-canonical nucleic acid structures regulating key cellular processes.
• G4 biological functions are linked to their thermostability, determined by specific sequence features.

Purpose of the Study:

• To systematically review evidence on sequence determinants of G4 thermostability.
• To integrate findings from biophysical and genomic studies for a unified framework.

Main Methods:

• Systematic synthesis of evidence from high-precision biophysical studies.
• Analysis of high-throughput genomic assays.

Main Results:

• G4 stability arises from G-tract core, loops, and flanking sequences.
• G-tract length and integrity are key, with exceptions like short G-tracts and bulges.
• Loop length inversely correlates with stability, influenced by composition and methods.
• Flanking sequences modulate stability and topology.

Conclusions:

• A unified framework connects biophysical and genomic observations of G4 stability.
• Understanding sequence determinants advances prediction of G4 stability, topology, and function.
• This knowledge is critical for understanding G4 roles in health and disease.