A general design strategy for protein-responsive riboswitches in mammalian cells

Ausländer, Simon; Stücheli, Pascal; Rehm, Charlotte; Ausländer, David; Hartig, Jörg S.; Fussenegger, Martin

A general design strategy for protein-responsive riboswitches in mammalian cells

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Date

2014

Authors

Ausländer, Simon

Stücheli, Pascal

Rehm, Charlotte

Ausländer, David

Hartig, Jörg S.

Fussenegger, Martin

DOI (citable link)

10.1038/nmeth.3136

Collections

Chemie

Publication type

Journal article

Published in

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.

Subject (DDC)

540 Chemistry

Keywords

Riboswitches, Synthetic biology, Gene regulation

Cite This

ISO 690

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.3136

BibTex

@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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Bibliography of Konstanz

Yes