Ribozymes and aptamers in the RNA world, and in synthetic biology

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The RNA world hypothesis postulates that Ribonucleic Acids (RNA) may have provided functions of catalysis and genetic information storage during the origin of life on earth. An RNA based life is hypothesized to have undergone Darwinian evolution to ultimately lead into extant biology, where DNA is used as the repository for genetic information and proteins are used as biological catalysts. The discovery of functional RNAs such as catalytic RNAs, regulatory RNAs, and ligand-binding RNA aptamers further strengthen this hypothesis. These functional RNAs are also used as tools for synthetic biology and therapeutics. This work highlights strategies used by RNA enzymes (Ribozymes) for catalysis of chemical reactions, and explores new chemistries catalyzed by ribozymes. We also engineered an in vitro evolved ribozyme to control activities of other functional RNA molecules. Finally, this work explores innovative approaches to discover new RNA enzymes that catalyze biologically relevant reactions. Findings from these studies have revealed potential roles of RNA enzymes during the primordial earth, and also opened doors to build RNA-based tools that regulate biological processes.