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Restoration of Ribozyme Tertiary Contact and Function by Using a Molecular Glue for RNA.
- Source :
-
Angewandte Chemie International Edition . 1/8/2018, Vol. 57 Issue 2, p506-510. 5p. - Publication Year :
- 2018
-
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]
- Subjects :
- *RNA
*NUCLEIC acids
*POLYPEPTIDES
*CARRIER proteins
*PROTEIN folding
Subjects
Details
- Language :
- English
- ISSN :
- 14337851
- Volume :
- 57
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Angewandte Chemie International Edition
- Publication Type :
- Academic Journal
- Accession number :
- 127191448
- Full Text :
- https://doi.org/10.1002/anie.201709041