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Prebiotically Plausible RNA Activation Compatible with Ribozyme‐Catalyzed Ligation
Author(s) -
Song Emilie Yeonwha,
Jiménez Eddy Ivanhoe,
Lin Huacan,
Le Vay Kristian,
Krishnamurthy Ramanarayanan,
Mutschler Hannes
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202010918
Subject(s) - ribozyme , rna , ligase ribozyme , oligonucleotide , chemistry , hairpin ribozyme , catalysis , combinatorial chemistry , biochemistry , dna , gene
RNA‐catalyzed RNA ligation is widely believed to be a key reaction for primordial biology. However, since typical chemical routes towards activating RNA substrates are incompatible with ribozyme catalysis, it remains unclear how prebiotic systems generated and sustained pools of activated building blocks needed to form increasingly larger and complex RNA. Herein, we demonstrate in situ activation of RNA substrates under reaction conditions amenable to catalysis by the hairpin ribozyme. We found that diamidophosphate (DAP) and imidazole drive the formation of 2′,3′‐cyclic phosphate RNA mono‐ and oligonucleotides from monophosphorylated precursors in frozen water‐ice. This long‐lived activation enables iterative enzymatic assembly of long RNAs. Our results provide a plausible scenario for the generation of higher‐energy substrates required to fuel ribozyme‐catalyzed RNA synthesis in the absence of a highly evolved metabolism.