Hydrophobic-cationic peptides modulate RNA polymerase ribozyme activity by accretion.

Accretion and the resulting increase in local concentration is a widespread mechanism in biology to enhance biomolecular functions (for example, in liquid-liquid demixing phases). Such macromolecular aggregation phases (e.g., coacervates, amyloids) may also have played a role in the origin of life. Here, we report that a hydrophobic-cationic RNA binding peptide selected by phage display (P43: AKKVWIIMGGS) forms insoluble amyloid-containing aggregates, which reversibly accrete RNA on their surfaces in an RNA-length and Mg 2+ -concentration dependent manner. The aggregates formed by P43 or its sequence-simplified version (K 2 V 6 : KKVVVVVV) inhibited RNA polymerase ribozyme (RPR) activity at 25 mM MgCl 2 , while enhancing it significantly at 400 mM MgCl 2 . Our work shows that such hydrophobic-cationic peptide aggregates can reversibly concentrate RNA and enhance the RPR activity, and suggests that they could have aided the emergence and evolution of longer and functional RNAs in the fluctuating environments of the prebiotic earth.