Extended structures in RNA folding intermediates are due to nonnative interactions rather than electrostatic...

Area of Science:

• Molecular Biology
• Biophysics

Background:

• RNA folding proceeds through intermediate states.
• These intermediates are typically less compact than native structures.
• Previous work showed the Bacillus subtilis RNase P RNA S-domain intermediate is extended.

Purpose of the Study:

• Investigate origins of extended intermediate structures in B. subtilis and E. coli RNase P RNA S-domains.
• Test models of electrostatic repulsion versus specific core interactions.
• Determine factors stabilizing RNA folding intermediates.

Main Methods:

• Small-angle X-ray scattering (SAXS)
• Langevin dynamics simulations

Main Results:

• Electrostatic repulsion plays a minor role in intermediate extension.
• Specific interactions, including nonnative base pairs, stabilize extended conformations.
• Short-range, nonnative contacts are key to intermediate structure.

Conclusions:

• Extended RNA folding intermediates result from specific, nonnative interactions.
• These findings are relevant to ribozymes and riboswitches.
• Principles apply to functionally relevant RNA conformational changes.