Amino acids catalyse RNA formation under ambient alkaline conditions
Abstract RNA and proteins are the foundation of life and a natural starting point to explore its origins. However, the prebiotic relationship between the two is asymmetric. While RNA evolved to assemble proteins from amino acids, a significant mirror-symmetric effect of amino acids to trigger the sy...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60359-3 |
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| author | Saroj K. Rout Sreekar Wunnava Miroslav Krepl Giuseppe Cassone Judit E. Šponer Christof B. Mast Matthew W. Powner Dieter Braun |
| author_facet | Saroj K. Rout Sreekar Wunnava Miroslav Krepl Giuseppe Cassone Judit E. Šponer Christof B. Mast Matthew W. Powner Dieter Braun |
| author_sort | Saroj K. Rout |
| collection | DOAJ |
| description | Abstract RNA and proteins are the foundation of life and a natural starting point to explore its origins. However, the prebiotic relationship between the two is asymmetric. While RNA evolved to assemble proteins from amino acids, a significant mirror-symmetric effect of amino acids to trigger the synthesis of RNA was missing. We describe ambient alkaline conditions where amino acids, without additional chemical activators, promote RNA copolymerisation more than 100-fold, starting from prebiotically plausible ribonucleoside-2′,3′-cyclic phosphates. The observed effect is explained by acid-base catalysis, with optimal efficiency at pH values near the amine pK aH. The fold-change in oligomerisation yield is nucleobase-selective, resulting in increased compositional diversity necessary for subsequent molecular evolution and favouring the formation of natural 3′−5′ linkages. The elevated pH offers recycling of oligonucleotide sequences back to 2′,3′-cyclic phosphates, providing conditions for high-fidelity replication by templated ligation. The findings reveal a clear functional role of amino acids in the evolution of RNA earlier than previously assumed. |
| format | Article |
| id | doaj-art-d4d4c91fa1dc41dca53c92f3c5a9ee17 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d4d4c91fa1dc41dca53c92f3c5a9ee172025-08-20T03:25:19ZengNature PortfolioNature Communications2041-17232025-06-011611910.1038/s41467-025-60359-3Amino acids catalyse RNA formation under ambient alkaline conditionsSaroj K. Rout0Sreekar Wunnava1Miroslav Krepl2Giuseppe Cassone3Judit E. Šponer4Christof B. Mast5Matthew W. Powner6Dieter Braun7Systems Biophysics and Center for NanoScience, Faculty of Physics, Ludwig-Maximilians-Universität MünchenSystems Biophysics and Center for NanoScience, Faculty of Physics, Ludwig-Maximilians-Universität MünchenInstitute of Biophysics of the Czech Academy of SciencesInstitute for Chemical-Physical Processes, National Research Council of Italy (IPCF-CNR)Institute of Biophysics of the Czech Academy of SciencesSystems Biophysics and Center for NanoScience, Faculty of Physics, Ludwig-Maximilians-Universität MünchenDepartment of Chemistry, University College LondonSystems Biophysics and Center for NanoScience, Faculty of Physics, Ludwig-Maximilians-Universität MünchenAbstract RNA and proteins are the foundation of life and a natural starting point to explore its origins. However, the prebiotic relationship between the two is asymmetric. While RNA evolved to assemble proteins from amino acids, a significant mirror-symmetric effect of amino acids to trigger the synthesis of RNA was missing. We describe ambient alkaline conditions where amino acids, without additional chemical activators, promote RNA copolymerisation more than 100-fold, starting from prebiotically plausible ribonucleoside-2′,3′-cyclic phosphates. The observed effect is explained by acid-base catalysis, with optimal efficiency at pH values near the amine pK aH. The fold-change in oligomerisation yield is nucleobase-selective, resulting in increased compositional diversity necessary for subsequent molecular evolution and favouring the formation of natural 3′−5′ linkages. The elevated pH offers recycling of oligonucleotide sequences back to 2′,3′-cyclic phosphates, providing conditions for high-fidelity replication by templated ligation. The findings reveal a clear functional role of amino acids in the evolution of RNA earlier than previously assumed.https://doi.org/10.1038/s41467-025-60359-3 |
| spellingShingle | Saroj K. Rout Sreekar Wunnava Miroslav Krepl Giuseppe Cassone Judit E. Šponer Christof B. Mast Matthew W. Powner Dieter Braun Amino acids catalyse RNA formation under ambient alkaline conditions Nature Communications |
| title | Amino acids catalyse RNA formation under ambient alkaline conditions |
| title_full | Amino acids catalyse RNA formation under ambient alkaline conditions |
| title_fullStr | Amino acids catalyse RNA formation under ambient alkaline conditions |
| title_full_unstemmed | Amino acids catalyse RNA formation under ambient alkaline conditions |
| title_short | Amino acids catalyse RNA formation under ambient alkaline conditions |
| title_sort | amino acids catalyse rna formation under ambient alkaline conditions |
| url | https://doi.org/10.1038/s41467-025-60359-3 |
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