RNAiFold2T: constraint programming design of thermo-IRES switches

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• dc.contributor.author Garcia-Martin, Juan Antonio
• dc.contributor.author Dotu, Ivan
• dc.contributor.author Fernandez-Chamorro, Javier
• dc.contributor.author Lozano, Gloria
• dc.contributor.author Ramajo, Jorge
• dc.contributor.author Martinez Salas, Encarnación
• dc.contributor.author Clote, Peter
• dc.date.accessioned 2024-01-15T09:47:28Z
• dc.date.available 2024-01-15T09:47:28Z
• dc.date.issued 2016
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract Motivation: RNA thermometers (RNATs) are cis -regulatory elements that change secondary structure upon temperature shift. Often involved in the regulation of heat shock, cold shock and virulence genes, RNATs constitute an interesting potential resource in synthetic biology, where engineered RNATs could prove to be useful tools in biosensors and conditional gene regulation. Results: Solving the 2-temperature inverse folding problem is critical for RNAT engineering. Here we introduce RNAiFold2T, the first Constraint Programming (CP) and Large Neighborhood Search (LNS) algorithms to solve this problem. Benchmarking tests of RNAiFold2T against existent programs (adaptive walk and genetic algorithm) inverse folding show that our software generates two orders of magnitude more solutions, thus allowing ample exploration of the space of solutions. Subsequently, solutions can be prioritized by computing various measures, including probability of target structure in the ensemble, melting temperature, etc. Using this strategy, we rationally designed two thermosensor internal ribosome entry site ( thermo -IRES) elements, whose normalized cap-independent translation efficiency is approximately 50% greater at 42 °C than 30 °C, when tested in reticulocyte lysates. Translation efficiency is lower than that of the wild-type IRES element, which on the other hand is fully resistant to temperature shift-up. This appears to be the first purely computational design of functional RNA thermoswitches, and certainly the first purely computational design of functional thermo-IRES elements.
• dc.description.sponsorship Research of the Clote Lab was supported by National Science Foundation grant [DBI-1262439]. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. Research of the Martinez-Salas Lab was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) [CSD2009-00080, BFU2011-25437, BFU2014-54564] and by an Institutional Grant from Fundación Ramón Areces.
• dc.format.mimetype application/pdf
• dc.identifier.citation Garcia-Martin JA, Dotu I, Fernandez-Chamorro J, Lozano G, Ramajo J, Martinez-Salas E, et al. RNAiFold2T: constraint programming design of thermo-IRES switches. Bioinformatics. 2016 Jun 15;32(12):i360-i368. DOI: 10.1093/bioinformatics/btw265
• dc.identifier.doi http://dx.doi.org/10.1093/bioinformatics/btw265
• dc.identifier.issn 1367-4811
• dc.identifier.uri http://hdl.handle.net/10230/58687
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Bioinformatics. 2016 Jun 15;32(12):i360-i368
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-25437
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-54564
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
• dc.rights © The Author 2016. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.other Termometria -- Aparells i instruments
• dc.subject.other Termòmetres
• dc.subject.other Virus
• dc.subject.other Bioinformàtica
• dc.title RNAiFold2T: constraint programming design of thermo-IRES switches
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion