Investigation of Phosphate-Based Reactions in the Context of an Evolving RNA World
In light of the unique ability of ribonucleic acid (RNA) to both retain genetic information and catalyze chemical reactions, it has been proposed that life on Earth progressed through an RNA world. It has been demonstrated that phosphate was present on an early Earth and due to the prevalence of modern-day energy metabolisms that rely on phosphorylation, it is likely that phosphate played a key role in prebiotic chemistry. This work characterizes a number of phosphate-based reactions ranging from formation of triphosphates to RNA repair. Chapter 1 introduces catalytic RNA and summarizes the main types of reactivities that have been discovered or evolved. Chapter 2 characterizes the reaction of cyclic trimetaphosphate with nucleosides to form nucleoside triphosphates in concentrations sufficient to sustain polymerization. Chapter 3 demonstrates the first known example of ribozyme-mediated repair of damaged and mismatched RNA sequences using pyrophosphate. Taken in concert, these reactions provide key insight into the potential role of phosphate in an evolving RNA world.