A self-replicating ligase ribozyme

TLDR

Self‑replicating molecules catalyze the covalent assembly of identical copies, and when the product can also catalyze its own formation the system is autocatalytic. The study aims to optimize the system to achieve sustained exponential growth of self‑replicating ribozymes. The authors engineered the R3C ligase ribozyme to ligate two substrates into an exact copy of itself, creating a self‑replicating system that relies on RNA catalysis. The ribozyme exhibited exponential growth with an autocatalytic rate constant of 0.011 min⁻¹, but growth was limited by reduced complex formation of newly formed copies.

Abstract

A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 min −1 , whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 × 10 −11 M⋅min −1 . Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication.