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Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression

Shensi Shen, Guillermo Rodrigo, Satya Prakash, Eszter Majer, Thomas E. Landrain, Boris Kirov, José-Antonio Daròs, View ORCID ProfileAlfonso Jaramillo
doi: https://doi.org/10.1101/016915
Shensi Shen
1 Institute of Systems and Synthetic Biology, Université d’Évry Val d’Essonne, CNRS, F-91000 Évry, France
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Guillermo Rodrigo
1 Institute of Systems and Synthetic Biology, Université d’Évry Val d’Essonne, CNRS, F-91000 Évry, France
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Satya Prakash
3 School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom
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Eszter Majer
2 Instituto de Biología Molecular y Celular de Plantas, CSIC - Universidad Politécnica de Valencia, 46022 Valencia, Spain
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Thomas E. Landrain
1 Institute of Systems and Synthetic Biology, Université d’Évry Val d’Essonne, CNRS, F-91000 Évry, France
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Boris Kirov
1 Institute of Systems and Synthetic Biology, Université d’Évry Val d’Essonne, CNRS, F-91000 Évry, France
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José-Antonio Daròs
2 Instituto de Biología Molecular y Celular de Plantas, CSIC - Universidad Politécnica de Valencia, 46022 Valencia, Spain
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Alfonso Jaramillo
1 Institute of Systems and Synthetic Biology, Université d’Évry Val d’Essonne, CNRS, F-91000 Évry, France
3 School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom
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  • ORCID record for Alfonso Jaramillo
  • For correspondence: Alfonso.Jaramillo@warwick.ac.uk
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Abstract

Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA-RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 23, 2015.
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Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression
Shensi Shen, Guillermo Rodrigo, Satya Prakash, Eszter Majer, Thomas E. Landrain, Boris Kirov, José-Antonio Daròs, Alfonso Jaramillo
bioRxiv 016915; doi: https://doi.org/10.1101/016915
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Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression
Shensi Shen, Guillermo Rodrigo, Satya Prakash, Eszter Majer, Thomas E. Landrain, Boris Kirov, José-Antonio Daròs, Alfonso Jaramillo
bioRxiv 016915; doi: https://doi.org/10.1101/016915

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