Defined folding pattern of poly(rG) supports inherent ability to encode biological information

Area of Science:

• Origin of Life studies
• Biochemistry
• Molecular Biology

Background:

• The RNA World hypothesis, while influential, faces challenges in explaining early life origins.
• The Quadruplex (G4) World hypothesis proposes poly(dG) forms stable G-tetrad architectures, offering a paradox-free alternative.
• Key questions remain regarding RNA's ability to form G-quadruplexes and their evolution towards Watson-Crick complementarity.

Purpose of the Study:

• To investigate if RNA shares the same G-quadruplex folding pattern as DNA.
• To explore how stable G-quadruplexes could evolve into the current information transfer system.
• To analyze the thermodynamic and optical properties of DNA and RNA G15/G3T sequences.

Main Methods:

• Systematic study of thermodynamic and optical properties.
• Analysis of DNA and RNA sequences derived from G15 and G3T motifs.
• Comparison of quadruplex formation and stability between DNA and RNA.

Main Results:

• Both DNA and RNA sequences adopt stable G-quadruplex structures with three G-tetrads and single-G loops.
• Poly(dG) and poly(rG) exhibit an inherent ability to fold into defined 3D quadruplex architectures.
• Single-nucleotide substitutions significantly destabilize both DNA and RNA G-quadruplexes, reducing thermal stability by ~40°C.

Conclusions:

• RNA, like DNA, possesses the intrinsic capability to form stable G-quadruplex structures, supporting the G4 World hypothesis.
• The vulnerability of these quadruplexes to mutations provides a potential mechanism for the introduction of complementarity.
• This research offers insights into early molecular evolution and the transition from G-quadruplex-based systems to modern genetic information transfer.