Iron responsive element RNA flexibility described by NMR and isotropic reorientational eigenmode dynamics

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• The Iron Responsive Element (IRE) is a small, flexible RNA hairpin crucial for iron regulation.
• Understanding the dynamics of such flexible RNA structures is challenging but essential for biological function.

Purpose of the Study:

• To apply Reorientational Eigenmode Dynamics (RED) to RNA for the first time, using the IRE hairpin as a model system.
• To compare RED-derived order parameters with experimental Nuclear Magnetic Resonance (NMR) data.
• To investigate the complex internal and global motions of the IRE RNA using RED and isotropic RED (iRED).

Main Methods:

• A 12 ns molecular dynamics trajectory of the IRE RNA hairpin was generated.
• Order parameters were calculated from the trajectory using RED and isotropic RED (iRED).
• Calculated order parameters were compared to experimentally determined parameters from 13C-1H NMR relaxation experiments.

Main Results:

• Order parameters from RED analysis showed qualitative agreement with experimental NMR data.
• iRED analysis revealed that global and internal dynamics of the IRE are not separable, potentially affecting experimental parameter accuracy.
• iRED successfully described correlated motions within the IRE RNA dynamics.

Conclusions:

• The study demonstrates the successful application of RED and iRED to analyze RNA dynamics.
• Combining RED/iRED with NMR relaxation provides a highly detailed description of IRE RNA dynamics.
• The findings highlight the complexity of dynamics in small, flexible RNA molecules.