Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements

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  • dc.contributor.author Fernandez-Chamorro, Javier
  • dc.contributor.author Lozano, Gloria
  • dc.contributor.author Garcia-Martin, Juan Antonio
  • dc.contributor.author Ramajo, Jorge
  • dc.contributor.author Dotu, Ivan
  • dc.contributor.author Clote, Peter
  • dc.contributor.author Martinez Salas, Encarnación
  • dc.date.accessioned 2023-12-19T06:47:19Z
  • dc.date.available 2023-12-19T06:47:19Z
  • dc.date.issued 2016
  • dc.description Supplementary materials files: online appendix; replication data.
  • dc.description.abstract The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems. Our data supports the hypothesis that structural sequestration of the pyrimidine-tract within a stable hairpin inactivates IRES activity, since the stronger the stability of the hairpin the higher the inhibition of protein synthesis. Destabilization of the stem-loop immediately upstream of the pyrimidine-tract also decreases IRES activity. Our work introduces a hybrid computational/experimental method to determine the importance of structural motifs for biological function. Specifically, we show the feasibility of using the software RNAiFold to design synthetic RNAs with particular sequence and structural motifs that permit subsequent experimental determination of the importance of such motifs for biological function.
  • dc.description.sponsorship We are grateful to S. Lopez de Quinto for early work on the FMDV IRES. This work 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 Fernandez-Chamorro J, Lozano G, Garcia-Martin JA, Ramajo J, Dotu I, Clote P, et al. Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements. Sci Rep. 2016 Apr 7;6(1):24243. DOI: 10.1038/srep24243
  • dc.identifier.doi http://dx.doi.org/10.1038/srep24243
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/58570
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Scientific Reports. 2016 Apr 7;6(1):24243
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-25437
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-54564
  • dc.rights This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Biologia computacional
  • dc.subject.other Bioinformàtica
  • dc.subject.other Genètica
  • dc.title Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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