Self-cleaving ribozymes: substrate specificity and synthetic biology applications

Abstract

Various self-cleaving ribozymes appearing in nature catalyze the sequence-specific intramolecular cleavage of RNA and can be engineered to catalyze cleavage of appropriate substrates in an intermolecular fashion, thus acting as true catalysts. The mechanisms of the small, self-cleaving ribozymes have been extensively studied and reviewed previously. Self-cleaving ribozymes can possess high catalytic activity and high substrate specificity; however, substrate specificity is also engineerable within the constraints of the ribozyme structure. While these ribozymes share a common fundamental catalytic mechanism, each ribozyme family has a unique overall architecture and active site organization, indicating that several distinct structures yield this chemical activity. The multitude of catalytic structures, combined with some flexibility in substrate specificity within each family, suggests that such catalytic RNAs, taken together, could access a wide variety of substrates. Here, we give an overview of 10 classes of self-cleaving ribozymes and capture what is understood about their substrate specificity and synthetic applications. Evolution of these ribozymes in an RNA world might be characterized by the emergence of a new ribozyme family followed by rapid adaptation or diversification for specific substrates.

Graphical abstract: Self-cleaving ribozymes: substrate specificity and synthetic biology applications

Article information

Article type
Review Article
Submitted
13 Nov 2020
Accepted
14 Jun 2021
First published
02 Jul 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021, Advance Article

Self-cleaving ribozymes: substrate specificity and synthetic biology applications

H. Peng, B. Latifi, S. Müller, A. Lupták and I. A. Chen, RSC Chem. Biol., 2021, Advance Article , DOI: 10.1039/D0CB00207K

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