1. Restoration of Ribozyme Tertiary Contact and Function by Using a Molecular Glue for RNA.
- Author
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Dohno, Chikara, Kimura, Maki, and Nakatani, Kazuhiko
- Subjects
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RNA , *NUCLEIC acids , *POLYPEPTIDES , *CARRIER proteins , *PROTEIN folding - Abstract
Some RNA classes require folding into the proper higher-order structures to exert their functions. Hammerhead ribozyme (HHR) requires a folding conformation stabilized by tertiary interaction for full activity. A rationally engineered HHR was developed that was inactive, but could be activated by a synthetic RNA-binding ligand, naphthyridine carbamate tetramer with Z-stilbene linker ( Z-NCTS). Binding of Z-NCTS could induce the formation of an active folding structure and thereby restore ribozyme activity, where Z-NCTS acts as a molecular glue to bring two isolated RNA loops into contact with each other. Next, we designed a Z-NCTS-responsive genetic switch using the HHR sequence inserted into the 3′ untranslated region as a cis-acting element. We demonstrated that the rationally designed ribozyme switch enabled regulation of gene expression by Z-NCTS and was functional in mammalian cells. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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