Ribozyme Chemistry: To Be or Not To Be under High Pressure

Area of Science:

• Biochemistry
• Molecular Biology
• Astrobiology

Background:

• High hydrostatic pressure (HHP) is a powerful tool for studying biomacromolecule structure-function relationships in solution.
• Osmotic pressure complements HHP by quantifying water exchange between macromolecules and solvent.
• Ribozymes, catalytic RNA molecules, are crucial for understanding RNA's role in early life.

Purpose of the Study:

• To review the influence of pressure on ribozyme chemistry and activity.
• To elucidate the pressure-induced mechanisms of self-cleavage in hairpin and hammerhead ribozymes.
• To explore the implications of these findings for the origins of RNA in prebiotic environments.

Main Methods:

• High hydrostatic pressure experiments to probe conformational changes and solvent interactions.
• Osmotic pressure measurements to determine water exchange volumes.
• Kinetic analysis of ribozyme self-cleavage reactions under varying pressure conditions.

Main Results:

• Pressure slows the self-cleavage reaction of the hairpin ribozyme, indicating a transition state involving water release (positive activation volume).
• The hammerhead ribozyme's self-cleaving activity is also reduced by pressure, with similar activation volumes, though evidence suggests molecular heterogeneity.
• Findings support the hypothesis that small, amino acid-binding ribozymes may have originated under extreme conditions, such as deep-sea vents.

Conclusions:

• Pressure-dependent studies provide precise insights into the volume changes and water dynamics governing ribozyme activity.
• The observed pressure effects on ribozyme self-cleavage offer mechanistic details relevant to their catalytic function.
• These results contribute to understanding the potential role of ribozymes in prebiotic chemistry under harsh environmental conditions.