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High-Yield Prebiotic Polymerization of 2',3'-Cyclic Nucleotides under Wet-Dry Cycling
Federico Caimi1, Juliette Langlais2, Francesco Fontana3
1Department of Medical Biotechnologies and Translational Medicine, University of Milan, via Fratelli Cervi 93, I-20090 Segrate, Milano, Italy.
ACS Central Science
|September 29, 2025
Summary
Early Earth conditions facilitated RNA polymer formation. Wet-dry cycling of cyclic nucleotides at mild alkaline pH led to efficient polymerization, crucial for the origin of life.
Area of Science:
- Prebiotic chemistry
- Origin of life studies
- RNA polymerization
Background:
- Spontaneous RNA polymer formation is key for life's origin.
- Prebiotic synthesis of RNA remains a significant challenge.
Purpose of the Study:
- To investigate efficient RNA polymerization under simulated early Earth conditions.
- To explore the role of wet-dry cycling in nucleotide polymerization.
Main Methods:
- Utilized 2',3'-cyclic nucleotides of all four nucleobases.
- Subjected nucleotides to wet-dry cycling at room temperature and mild alkaline pH.
- Employed microscopy to monitor polymerization during drying.
Main Results:
- Achieved high oligomerization yields (Y ≈ 70% for guanosine, Y ≥ 20% for others) via wet-dry cycling.
- Observed pH-dependent polymerization: guanosine self-assembly at pH ≤ 10 enhanced reactivity.
- At pH 11, achieved balanced polymerization of all four nucleotides (Y = 36%) forming mixed sequence oligomers.
Conclusions:
- Wet-dry cycling provides a viable pathway for prebiotic RNA synthesis.
- The process mimics early Earth's humid nights and dry days.
- Generated mixed sequence RNA oligomers, supporting RNA replication and evolution models.
