Tailoring RNA modular units on a common scaffold: A modular ribozyme with a catalytic unit for β-nicotinamide mononucleotide-activated RNA ligation

Abstract

A novel ribozyme that accelerates the ligation of b-nicotinamide mononucleotide (β-NMN)-activated RNA fragments was isolated and characterized. This artificial ligase ribozyme (YFL ribozyme) was isolated by a ''design and selection'' strategy, in which a modular catalytic unit was generated on a rationally designed modular scaffold RNA. Biochemical analyses of the YFL ribozyme revealed that it catalyzes RNA ligation in a template-dependent manner, and its activity is highly dependent on its architecture, which consists of a modular scaffold and a catalytic unit. As the design and selection strategy was used for generation of DSL ribozyme, isolation of the YFL ribozyme indicated the versatility of this strategy for generation of functional RNAs with modular architectures. The catalytic unit of the YFL ribozyme accepts not only b-NMN but also inorganic pyrophosphate and adenosine monophosphate as leaving groups for RNA ligation. This versatility of the YFL ribozyme provides novel insight into the possible roles of β-NMN (or NADH) in the RNA world. Copyright © 2009 RNA Society.