RNA‐Catalyzed RNA Ligation within Prebiotically Plausible Model Protocells**

Abstract

AbstractDemonstrating RNA catalysis within prebiotically relevant models of primordial cells (protocells) remains a challenge in origins of life research. Fatty acid vesicles encapsulating genomic and catalytic RNAs (ribozymes) are attractive models for protocells; however, RNA catalysis has largely been incompatible with fatty acid vesicles due to their instability in the presence of Mg2+ at the concentrations required for ribozyme function. Here, we report a ribozyme that catalyzes template‐directed RNA ligation at low Mg2+ concentrations and thus remains active within stable vesicles. Ribose and adenine, both prebiotically relevant molecules, were found to greatly reduce Mg2+‐induced RNA leakage from vesicles. When we co‐encapsulated the ribozyme, substrate, and template within fatty acid vesicles, we observed efficient RNA‐catalyzed RNA ligation upon subsequent addition of Mg2+. Our work shows that RNA‐catalyzed RNA assembly can occur efficiently within prebiotically plausible fatty acid vesicles and represents a step toward the replication of primordial genomes within self‐replicating protocells.