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Updated: Jul 15, 2026

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Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
A ribozyme ligase that requires a 3' terminal phosphate on its RNA substrate
Annyesha Biswas1, Zoe Weiss2, Jack W Szostak3,4
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.
Nature Communications
|July 13, 2026
Summary
Researchers discovered novel ribozyme ligases that repair RNA by joining broken strands with a 3'-phosphate group. These ribozymes could have been crucial for RNA repair in early life and have applications in modern RNA sequencing.
Area of Science:
- Biochemistry
- Molecular Biology
- Origin of Life Studies
Background:
- Ribozymes were crucial for early RNA-based life, catalyzing metabolic and replication processes.
- In vitro evolution has expanded the known catalytic abilities of RNA.
- Understanding primordial RNA repair mechanisms is key to understanding early life evolution.
Purpose of the Study:
- To report the discovery of novel ribozyme ligases with unique substrate specificities.
- To investigate the potential role of these ribozymes in primordial RNA repair.
- To explore the utility of these ribozymes in modern molecular biology techniques like transcriptomics.
Main Methods:
- In vitro evolution to discover new ribozyme activities.
- Biochemical assays to characterize ribozyme ligase activity and substrate specificity.
- Demonstration of selective ligation to 3 -phosphorylated RNA in mixed cellular RNA samples.
- Application of ribozymes for capturing and amplifying cleaved RNA fragments.
Main Results:
- Discovery of ribozyme ligases that catalyze the ligation of RNA substrates possessing a 3 -phosphate group.
- The discovered ribozymes specifically ligate 3 -phosphorylated RNA within complex mixtures.
- Ribozymes can capture and amplify cleaved RNA fragments with specific phosphate termini.
- These ribozymes show potential as enrichment reagents for RNA cleavage product analysis.
Conclusions:
- Ribozyme-catalyzed ligation of 3 -phosphorylated RNA may represent a primordial RNA repair pathway.
- The discovered ribozymes offer a new tool for selective RNA manipulation and analysis.
- Findings provide insights into ribozyme evolution and potential applications in RNA sequencing and transcriptomics.
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