Dr. Darrin York

Rutgers – School of Arts and Sciences
Department of Chemistry and Chemical Biology

Friday, October 27, 2023
12:00 Noon
Room 120 – Meyerhoff Chemistry Building
Host: Dr. Deepak Koirala

“How ribozymes work: mechanistic strategies of natural and artificially engineered RNA enzymes“

RNA enzymes, or “ribozymes”, use unique strategies to maximize the reactivity of their limited chemical library of four nucleobases in order to catalyze a wide range of reactions.  Naturally occurring small self-cleaving ribozymes catalyze site-specific phosphoryl transfer reactions that are fundamental in biology [1,2]. In the context of the RNA world hypothesis, these reactions are potentially evolutionary vestiges of chemical functions that have since been overtaken by proteins, begging the question of whether ancient RNAs once had the ability to catalyze more diverse reactions as precursors to modern protein counterparts, and how their mechanistic strategies may be reflected in modern biology. Evaluating this catalytic range is critical to rationalize evolutionary theories and may also shed light onto relationships between ribozyme classes, and between ribozymes and riboswitches. This talk discusses advancements in our understanding of ribozyme catalysis in the context of the mechanistic strategies of several naturally occurring ribozyme classes [3-5], as well as recently characterized artificially engineered RNA (and DNA) enzymes [6,7].   A common L-platform/L-scaffold framework is identified that provides a blueprint for design of RNA-cleaving nucleic acid enzymes [8].  Basic mechanistic strategies that enable RNA strand cleavage in natural ribozymes have been observed to be transferred to artificial DNAzymes [6] and ribozymes that can catalyze alkyl transfer [7]. The insight gained from these studies provides a predictive-level understanding of mechanisms that can be used to guide the design of new RNA and DNA enzymes.