Origin & Evolution of Life

RNA-catalyzed RNA Ligation Within Prebiotically Plausible Model Protocells

By Keith Cowing
Status Report
February 11, 2023
Filed under , , , , , , , ,
RNA-catalyzed RNA Ligation Within Prebiotically Plausible Model Protocells
Ribozyme retention within fatty acid vesicles in presence of Mg2+ . A. 5 µM FAM-labeled ligase ribozyme (RS8_trunc; for secondary structure and sequence, see Figure 1A, Supplementary Table S1) was encapsulated within DA/DOH/GMD (4:1:1) vesicles and 2 mM or 3 mM Mg2+ was added to its exterior. B. Leakage of FAM-labeled ribozyme from vesicles was followed over 3 h. Negligible leakage was observed in the absence of Mg2+ and ~30% leakage was observed in the presence of 2 or 3 mM Mg2+ after 3 h. C, D. Representative confocal micrographs of DA/DOH/GMD vesicles containing a FAM-labeled ligase ribozyme in the presence of 3 mM Mg2+. Membranes were stained using Rhodamine B (red). Vesicles at (C) t = 0 and (D) t = 3 h. Scale bars represent 5 µm. — biorxiv.org

Demonstrating 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 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.

Saurja DasGupta[a], Stephanie J. Zhang[a], Merrick P. Smela[b], Jack W.

full paper


Explorers Club Fellow, ex-NASA Space Station Payload manager/space biologist, Away Teams, Journalist, Lapsed climber, Synaesthete, Na’Vi-Jedi-Freman-Buddhist-mix, ASL, Devon Island and Everest Base Camp veteran, (he/him) 🖖🏻