Aug 25 – 27, 2021
Online
Europe/Berlin timezone

Coupling ribozyme catalyzed ligation and recombination with heterogeneous reaction environments

Aug 27, 2021, 11:25 AM
25m
Online

Online

Due to unstable situation with Covid-19 the event will be held online!

Speaker

Hannes Mutschler (MPI of Biochemistry)

Description

Enzymatic ligation and recombination of nucleic acids are key reactions required for both self-replication and the emergence of complex sequence information. It is therefore very likely that these reactions played a fundamental role in early stages of biology. We use different ribozyme systems as models to mimic how these reactions might have proceeded under heterogeneous reaction conditions on the early Earth. While direct ligation of oligonucleotides such as RNA requires activated substrate pools, typical chemical methods for robust and continuous substrate activation are incompatible with ribozyme catalysis. We explore scenarios for the in-situ activation of RNA substrates under reaction conditions amenable to catalysis by ligase ribozymes. We find 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 increasingly larger RNAs. We also demonstrate how RNA cleavage/ligation-based recombination reactions benefit dramatically from the presence of charged co-polymers, which enable the assembly of complex RNA structures from short oligonucleotides under isothermal, low-salt conditions. In summary, chemically diverse environments can help primitive nucleic acid catalysts bridge the gap between pools of short oligomers and functional RNAs.

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