## A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression

2010
Ausländer, Simon
Ketzer, Patrick
Journal article
##### Published in
Molecular BioSystems ; 6 (2010), 5. - pp. 807-814. - ISSN 1742-206X. - eISSN 1742-2051
##### Abstract
The possibility to externally control gene expression is of fundamental importance in both basic and applied life sciences. Although there are some techniques available to regulate expression in mammalian cells, they rely on the presence of ligand-sensing transcription factors, making it necessary to generate cell lines or organisms that stably express these regulatory factors. In recent years, mechanisms relying on direct RNA-ligand interactions for controlling gene expression have been both discovered in nature and engineered artificially. Among the latter, RNA switches relying on catalytically active RNA have been described. In principle, ligand-dependent triggering of mRNA self-cleavage should be a universal mechanism in order to control gene expression in a variety of organisms. Nevertheless, no examples of such aptazymes acting as RNA-based switches have been reported so far in mammalian cells. Here we present the theophylline-induced activation of an mRNA-based hammerhead ribozyme, resulting in an off-switch of gene expression. Starting from an artificial aptazyme switch reported to function in bacteria, we identified and optimized important parameters such as artificial start codons and the communicating sequence connecting ribozyme and aptamer, resulting in an RNA switch that allows for controlling transgenic expression in mammalian cells without the need to express a corresponding ligand-sensing transcription factor.
540 Chemistry
##### Cite This
ISO 690AUSLÄNDER, Simon, Patrick KETZER, Jörg S. HARTIG, 2010. A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression. In: Molecular BioSystems. 6(5), pp. 807-814. ISSN 1742-206X. eISSN 1742-2051. Available under: doi: 10.1039/b923076a
BibTex
@article{Auslander2010ligan-9790,
year={2010},
doi={10.1039/b923076a},
title={A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression},
number={5},
volume={6},
issn={1742-206X},
journal={Molecular BioSystems},
pages={807--814},
author={Ausländer, Simon and Ketzer, Patrick and Hartig, Jörg S.}
}

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<dcterms:abstract xml:lang="eng">The possibility to externally control gene expression is of fundamental importance in both basic and applied life sciences. Although there are some techniques available to regulate expression in mammalian cells, they rely on the presence of ligand-sensing transcription factors, making it necessary to generate cell lines or organisms that stably express these regulatory factors. In recent years, mechanisms relying on direct RNA-ligand interactions for controlling gene expression have been both discovered in nature and engineered artificially. Among the latter, RNA switches relying on catalytically active RNA have been described. In principle, ligand-dependent triggering of mRNA self-cleavage should be a universal mechanism in order to control gene expression in a variety of organisms. Nevertheless, no examples of such aptazymes acting as RNA-based switches have been reported so far in mammalian cells. Here we present the theophylline-induced activation of an mRNA-based hammerhead ribozyme, resulting in an off-switch of gene expression. Starting from an artificial aptazyme switch reported to function in bacteria, we identified and optimized important parameters such as artificial start codons and the communicating sequence connecting ribozyme and aptamer, resulting in an RNA switch that allows for controlling transgenic expression in mammalian cells without the need to express a corresponding ligand-sensing transcription factor.</dcterms:abstract>
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