Paths to constructive processes in RNA-based early life

Song Wratil, Yeonwha (2022): Paths to constructive processes in RNA-based early life. Dissertation, LMU München: Faculty of Biology

Abstract

The work presented in this thesis aimed to bridge missing gaps in our knowledge of the emergence of primitive nucleic acid-based lifeforms. Specifically, I demonstrate two prebiotically plausible means by which longer and more complex RNA may have formed from pools of short oligomers. Firstly, I reconcile the remarkable utility of a phosphate source, diamidophosphate (DAP), in stably activating oligoribonucleotides under mild aqueous conditions amenable to the activity of the hairpin ribozyme. The reported approach provides long-lived 2’,3’-cyclic phosphate oligomers whose hydrolysis products can be reactivated over weeks in a one-pot reaction. This stands in contrast to conventional laboratory methods that generate potent and short-lived activated RNA substrates to drive constructive processes such as polymerization and recombination. Secondly, while the candidacy of phase-separated droplets as a primitive protocellular environment has long been proposed, only destructive ribozyme catalysis such as cleavage of substrate RNA has thus far been shown therein. Here, I demonstrate robust and versatile constructive ribozyme activity within droplets formed from simple cationic peptides and short oligomers. In both investigations, I report the assembly of a complex >180 nt RNA polymerase ribozyme from simple <30 nt oligomers. Taken together, the described work advances our understanding of how constructive nucleic acid-based processes toward molecular evolution and – eventually – life may have occurred.

• Item Type: Theses (Dissertation, LMU Munich)
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 570 Life sciences
• Faculties: Faculty of Biology
• Language: English
• Date of oral examination: 22. December 2022
• 1. Referee: Jungmann, Ralf
• Signature of the printed copy: 0001/UMC 29339