A general design strategy for protein-responsive riboswitches in mammalian cells
A general design strategy for protein-responsive riboswitches in mammalian cells
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2014
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Nature Methods ; 11 (2014). - pp. 1154-1160. - ISSN 1548-7091. - eISSN 1548-7105
Abstract
RNAs are ideal for the design of gene switches that can monitor and program cellular behavior because of their high modularity and predictable structure-function relationship. We have assembled an expression platform with an embedded modular ribozyme scaffold that correlates self-cleavage activity of designer ribozymes with transgene translation in bacteria and mammalian cells. A design approach devised to screen ribozyme libraries in bacteria and validate variants with functional tertiary stem-loop structures in mammalian cells resulted in a designer ribozyme with a protein-binding nutR-boxB stem II and a selected matching stem I. In a mammalian expression context, this designer ribozyme exhibited dose-dependent translation control by the N-peptide, had rapid induction kinetics and could be combined with classic small molecule–responsive transcription control modalities to construct complex, programmable genetic circuits.
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540 Chemistry
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Riboswitches, Synthetic biology, Gene regulation
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AUSLÄNDER, Simon, Pascal STÜCHELI, Charlotte REHM, David AUSLÄNDER, Jörg S. HARTIG, Martin FUSSENEGGER, 2014. A general design strategy for protein-responsive riboswitches in mammalian cells. In: Nature Methods. 11, pp. 1154-1160. ISSN 1548-7091. eISSN 1548-7105. Available under: doi: 10.1038/nmeth.3136BibTex
@article{Auslander2014gener-30093, year={2014}, doi={10.1038/nmeth.3136}, title={A general design strategy for protein-responsive riboswitches in mammalian cells}, volume={11}, issn={1548-7091}, journal={Nature Methods}, pages={1154--1160}, author={Ausländer, Simon and Stücheli, Pascal and Rehm, Charlotte and Ausländer, David and Hartig, Jörg S. and Fussenegger, Martin} }
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