Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.

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 p...

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Autores principales:	Guillermo Rodrigo, Thomas E Landrain, Eszter Majer, José-Antonio Daròs, Alfonso Jaramillo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/36ff29ef71b04a09b075c750b2a94d3a
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spelling	oai:doaj.org-article:36ff29ef71b04a09b075c750b2a94d3a2021-11-18T05:53:41ZFull design automation of multi-state RNA devices to program gene expression using energy-based optimization.1553-734X1553-735810.1371/journal.pcbi.1003172https://doaj.org/article/36ff29ef71b04a09b075c750b2a94d3a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935479/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Small 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.Guillermo RodrigoThomas E LandrainEszter MajerJosé-Antonio DaròsAlfonso JaramilloPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 8, p e1003172 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Guillermo Rodrigo Thomas E Landrain Eszter Majer José-Antonio Daròs Alfonso Jaramillo Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.
description	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.
format	article
author	Guillermo Rodrigo Thomas E Landrain Eszter Majer José-Antonio Daròs Alfonso Jaramillo
author_facet	Guillermo Rodrigo Thomas E Landrain Eszter Majer José-Antonio Daròs Alfonso Jaramillo
author_sort	Guillermo Rodrigo
title	Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.
title_short	Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.
title_full	Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.
title_fullStr	Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.
title_full_unstemmed	Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.
title_sort	full design automation of multi-state rna devices to program gene expression using energy-based optimization.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/36ff29ef71b04a09b075c750b2a94d3a
work_keys_str_mv	AT guillermorodrigo fulldesignautomationofmultistaternadevicestoprogramgeneexpressionusingenergybasedoptimization AT thomaselandrain fulldesignautomationofmultistaternadevicestoprogramgeneexpressionusingenergybasedoptimization AT esztermajer fulldesignautomationofmultistaternadevicestoprogramgeneexpressionusingenergybasedoptimization AT joseantoniodaros fulldesignautomationofmultistaternadevicestoprogramgeneexpressionusingenergybasedoptimization AT alfonsojaramillo fulldesignautomationofmultistaternadevicestoprogramgeneexpressionusingenergybasedoptimization
_version_	1718424659285770240

Full design automation of multi-state RNA devices to program gene expression using energy-based optimization.

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