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Updated: Jul 23, 2025

Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
Triplet-Encoded Prebiotic RNA Aminoacylation
Meng Su1, Christian Schmitt2, Ziwei Liu1
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Before enzymes, RNA could be selectively aminoacylated without them. This study shows sequence-dependent, enzyme-free aminoacylation of RNA, suggesting a second genetic code in the RNA acceptor stem.
Area of Science:
- Origin of life studies
- Molecular biology
- Biochemistry
Background:
- Translation requires amino acids attached to tRNAs by aminoacyl-tRNA synthetases.
- The origin of this selective aminoacylation before enzyme evolution is unknown.
Purpose of the Study:
- To investigate enzyme-free, sequence-dependent aminoacylation of RNA.
- To explore potentially prebiotic routes for primordial tRNA aminoacylation.
Main Methods:
- Investigated two prebiotic routes for aminoacyl-tRNA acceptor stem-overhang mimics.
- Analyzed oligonucleotide efficiency in aminoacylation.
- Examined chemoselectivity and stereoselectivity of aminoacylation from mixed anhydride donors.
Main Results:
- Demonstrated enzyme-free, chemoselective aminoacylation of RNA.
- Overhang sequences had minimal impact on chemoselectivity.
- Aminoacylation selectivity depended on the terminal three base pairs of the RNA stem.
Conclusions:
- Supports the hypothesis of a second genetic code within the RNA acceptor stem.
- Provides insight into early RNA-based amino acid activation mechanisms.
- Suggests a plausible pathway for the origin of genetic coding.
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