Hydrophobic-cationic peptides modulate RNA polymerase ribozyme activity by accretion

Area of Science:

• Biochemistry
• Origin of Life Research
• RNA Biology

Background:

• Macromolecular aggregation phases, such as coacervates and amyloids, are crucial for enhancing biomolecular functions through local concentration.
• These aggregation phases may have played a significant role in the origin of life on early Earth.

Purpose of the Study:

• To investigate the RNA-binding properties and functional impact of a selected hydrophobic-cationic peptide (P43).
• To explore the potential role of such peptide-RNA interactions in the prebiotic environment for RNA evolution.

Main Methods:

• Selection of a hydrophobic-cationic RNA binding peptide (P43) using phage display.
• Characterization of P43's aggregation behavior and RNA accretion properties.
• Assay of RNA polymerase ribozyme (RPR) activity in the presence of P43 aggregates under varying MgCl2 concentrations.

Main Results:

• The P43 peptide forms insoluble amyloid-containing aggregates that reversibly bind RNA.
• RNA accretion is dependent on RNA length and Mg2+ concentration.
• P43 aggregates inhibited RPR activity at 25 mM MgCl2 but significantly enhanced it at 400 mM MgCl2.

Conclusions:

• Hydrophobic-cationic peptide aggregates can reversibly concentrate RNA and modulate enzyme activity.
• These findings suggest a plausible mechanism for concentrating and enhancing RNA function in fluctuating prebiotic environments.
• Such peptide-RNA interactions could have facilitated the emergence and evolution of longer, functional RNA molecules.