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

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Shen, Shensi, Rodrigo, Guillermo, Prakash, Satya, Majer, Eszter, Landrain, Thomas E., Kiro, Boris, Daros, Jose-Antonio and Jaramillo, Alfonso (2015) Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression. Nucleic Acids Research, 43 (10). pp. 5158-5170. doi:10.1093/nar/gkv287

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Official URL: http://dx.doi.org/10.1093/nar/gkv287

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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.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Genetic regulation, Catalytic RNA
Journal or Publication Title: Nucleic Acids Research
Publisher: Oxford University Press
ISSN: 0305-1048
Official Date: 26 May 2015
Dates:
DateEvent
26 May 2015Published
27 April 2015Available
24 March 2015Accepted
19 June 2014Submitted
Volume: 43
Number: 10
Number of Pages: 13
Page Range: pp. 5158-5170
DOI: 10.1093/nar/gkv287
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Seventh Framework Programme (European Commission) (FP7), Spain. Ministerio de Economía y Competitividad [Ministry of Economy and Competitiveness] (MINECO), Marie Curie Fellowship Association (MCFA), AXA Group. Research Fund, Spain. Ministerio de Educación y Ciencia (MEC)
Grant number: FP7-ICT-610730 (FP7), FP7-KBBE- 613745 (FP7), BIO2011-2674 (MINECO), ALTF-1177-2011, AP2012-3751 (MEC)

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