Coacervates protect RNA against hydrolysis under wet-dry cycling conditions

RNA is crucial to all extant biology and thought to have played an essential role in life’s origins. However, hydrolysis of RNA under common environmental conditions such as heating, drying, and exposure to divalent cations presents challenges for its persistence and effectiveness in prebiotic contexts. RNAs with less stable secondary and tertiary structures are especially susceptible to degradation. In living cells, sequestration in biopolymer-rich membraneless organelles helps shield RNA from damage and enzymatic degradation. Here, we report that compartmentalization into polyelectrolyte-based complex coacervate droplets protects RNA from hydrolysis during wet-dry cycling at elevated temperatures in the presence of Mg ²⁺ . This protection can be understood in terms of the coacervate microenvironment under varied salt concentrations and how it changes during sample drying. After gaining insight into this prebiotically-plausible mechanism using an unstructured model RNA, we demonstrate coacervate-based protection of a ligase ribozyme, supporting the functional relevance of the protection.