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Published on: July 5, 2024
Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation
Frank R Bowler1, Christopher K W Chan, Colm D Duffy
1Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Nature Chemistry
|April 24, 2013
Summary
Researchers discovered a new method for creating RNA polymers from simpler molecules, crucial for understanding the origin of life. This prebiotic chemistry enables efficient RNA chain formation, suggesting a plausible pathway for early life.
Area of Science:
- Astrobiology and Origin of Life Research
- Prebiotic Chemistry and Molecular Evolution
Background:
- The synthesis of ribonucleic acid (RNA) monomers under prebiotic conditions supports RNA's role in early life.
- A key challenge has been the prebiotic formation of long, 3',5'-linked RNA polymers from these monomers.
Purpose of the Study:
- To investigate a novel prebiotic chemical pathway for efficient RNA polymerization.
- To demonstrate the formation of predominantly 3',5'-linked RNA from activated ribonucleoside precursors.
Main Methods:
- Chemoselective acetylation of the 2'-hydroxyl group of oligoribonucleotide-3'-phosphates in water.
- Template-directed ligation of acetylated monomers under prebiotically plausible conditions.
- Selective deacetylation of the 2'-O-acetyl group post-ligation.
Main Results:
- Efficient and rapid template-directed ligation of RNA oligomers was achieved via 2'-O-acetylation.
- The 2'-O-acetyl protecting group was selectively removed without damaging internucleotide bonds.
- Acetylation demonstrated selectivity for the 2'-hydroxyl group of 2'- or 3'-terminal phosphates.
Conclusions:
- A new prebiotic route to predominantly 3',5'-linked RNA has been established.
- This chemistry provides a plausible pathway from ribonucleoside-2',3'-cyclic phosphates to functional RNA polymers.
- The findings strengthen the hypothesis of RNA's involvement in the origin of life.

