Solution structure of an unusually stable RNA tetraplex containing G- and U-quartet structures

Area of Science:

• Biochemistry
• Structural Biology
• Nucleic Acid Chemistry

Background:

• RNA tetraplexes are G-rich structures with potential biological significance.
• Understanding the structural diversity and stability of RNA tetraplexes is crucial for their functional characterization.

Purpose of the Study:

• To determine the solution structure of the RNA tetraplex (rUGGGGU)4.
• To investigate the stability and base-pairing interactions within the tetraplex.
• To provide evidence for the existence of U-quartet structures in RNA.

Main Methods:

• Two-dimensional Nuclear Magnetic Resonance (2D NMR) spectroscopy was employed to study the RNA tetraplex.
• Molecular dynamics simulations were used to model the solution structure.
• Stability was assessed by measuring the exchange half-lives of imino protons.

Main Results:

• A parallel-stranded RNA tetraplex structure with Hoogsteen base-pairing was elucidated.
• The tetraplex demonstrated high stability, evidenced by the long exchange half-lives of imino protons.
• The structure was stabilized by base stacking and hydrogen bonds within four G quartets and at least one U quartet.
• This study provides the first evidence for U-quartet formation in RNA.

Conclusions:

• The RNA tetraplex (rUGGGGU)4 adopts a stable, parallel-stranded structure in solution.
• The presence of a U-quartet represents a novel structural motif in RNA tetraplexes.
• These findings expand our understanding of RNA structural diversity and stability.