Nov 22 – 25, 2021
Kloster Irsee,
Europe/Berlin timezone

RNA catalysis in heterogeneous reaction environments

Nov 25, 2021, 2:00 PM
Kloster Irsee,

Kloster Irsee,


Hannes Mutschler (TU Dortmund)


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 positively charged peptide sequences, which enable the assembly of complex RNA structures from short oligonucleotides under isothermal, low-salt conditions. In summary, chemically diverse environments and primitive peptides can help nucleic acid catalysts to bridge the gap between pools of short oligomers and functional RNAs.

Presentation materials

There are no materials yet.