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Full design automation of multi-state RNA devices to program gene expression using energy-based optimization
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Rodrigo, Guillermo, Landrain, Thomas E., Majer, Eszter, Daròs, José-Antonio and Jaramillo, Alfonso (2013) Full design automation of multi-state RNA devices to program gene expression using energy-based optimization. PLoS Computational Biology, 9 (8). pp. 1-11. e1003172. doi:10.1371/journal.pcbi.1003172 ISSN 1553-7358.
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Official URL: http://dx.doi.org/10.1371/journal.pcbi.1003172
Abstract
Small RNAs (sRNAs) can operate as regulatory agents to control protein expression by interaction with the 5′ untranslated region of the mRNA. We have developed a physicochemical framework, relying on base pair interaction energies, to design multi-state sRNA devices by solving an optimization problem with an objective function accounting for the stability of the transition and final intermolecular states. Contrary to the analysis of the reaction kinetics of an ensemble of sRNAs, we solve the inverse problem of finding sequences satisfying targeted reactions. We show here that our objective function correlates well with measured riboregulatory activity of a set of mutants. This has enabled the application of the methodology for an extended design of RNA devices with specified behavior, assuming different molecular interaction models based on Watson-Crick interaction. We designed several YES, NOT, AND, and OR logic gates, including the design of combinatorial riboregulators. In sum, our de novo approach provides a new paradigm in synthetic biology to design molecular interaction mechanisms facilitating future high-throughput functional sRNA design.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QH Natural history | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Gene expression | ||||||||
Journal or Publication Title: | PLoS Computational Biology | ||||||||
Publisher: | Public Library of Science | ||||||||
ISSN: | 1553-7358 | ||||||||
Official Date: | 1 August 2013 | ||||||||
Dates: |
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Volume: | 9 | ||||||||
Number: | 8 | ||||||||
Number of Pages: | 11 | ||||||||
Page Range: | pp. 1-11 | ||||||||
Article Number: | e1003172 | ||||||||
DOI: | 10.1371/journal.pcbi.1003172 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Funder: | Seventh Framework Programme (European Commission) (FP7), Spain. Ministerio de Economía y Competitividad [Ministry of Economy and Competitiveness] (MINECO), AXA Group. Research Fund, Marie Curie Actions | ||||||||
Grant number: | 043338 (FP7), BIO2011-26741 (MINECO) |
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