Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection

Autores
Gismondi, Maria Ines; Ortiz, Xoana P.; Currá, Anabella Paola; Asurmendi, Sebastian; Taboga, Oscar Alberto
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
RNA interference (RNAi) appears as a promising strategy to control virus replication. While the antiviral power of short-hairpin RNAs or small-interfering RNAs against FMDV has been demonstrated widely, safer RNAi effectors such as artificial microRNAs (amiRs) have not been evaluated extensively. In this work, transgenic monoclonal cell lines constitutively expressing different amiRs targeting FMDV 3D-coding region or 3´UTR were established. Certain cell lines showed an effective, sequence-specific amiR-mediated silencing activity that was accomplished by degradation of the target mRNA, as demonstrated in co-transfection experiments of reporter genes fused to FMDV target sequences. However, FMDV replication in these amiR-expressing cells was affected barely. Experiments aimed at elucidating the cause of RNAi failure demonstrated limited accessibility of the targeted region in the molecular environment of the viral RNA. Since RNAi is mediated by large-dimension silencing complexes containing the siRNA and not simply by a linear oligonucleotide, we propose that target selection should consider not only the local RNA structure but also the global conformation of target RNA.
Fil: Gismondi, Maria Ines. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ortiz, Xoana P.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Currá, Anabella Paola. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Asurmendi, Sebastian. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Taboga, Oscar Alberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Artificial Micrornas
Antiviral
Fmdv
Accessibility
Rna Structure
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/33657
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/33657
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selectionGismondi, Maria InesOrtiz, Xoana P.Currá, Anabella PaolaAsurmendi, SebastianTaboga, Oscar AlbertoArtificial MicrornasAntiviralFmdvAccessibilityRna Structurehttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/4.4https://purl.org/becyt/ford/4RNA interference (RNAi) appears as a promising strategy to control virus replication. While the antiviral power of short-hairpin RNAs or small-interfering RNAs against FMDV has been demonstrated widely, safer RNAi effectors such as artificial microRNAs (amiRs) have not been evaluated extensively. In this work, transgenic monoclonal cell lines constitutively expressing different amiRs targeting FMDV 3D-coding region or 3´UTR were established. Certain cell lines showed an effective, sequence-specific amiR-mediated silencing activity that was accomplished by degradation of the target mRNA, as demonstrated in co-transfection experiments of reporter genes fused to FMDV target sequences. However, FMDV replication in these amiR-expressing cells was affected barely. Experiments aimed at elucidating the cause of RNAi failure demonstrated limited accessibility of the targeted region in the molecular environment of the viral RNA. Since RNAi is mediated by large-dimension silencing complexes containing the siRNA and not simply by a linear oligonucleotide, we propose that target selection should consider not only the local RNA structure but also the global conformation of target RNA.Fil: Gismondi, Maria Ines. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ortiz, Xoana P.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Currá, Anabella Paola. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Asurmendi, Sebastian. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Taboga, Oscar Alberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2014-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/33657Taboga, Oscar Alberto; Currá, Anabella Paola; Gismondi, Maria Ines; Asurmendi, Sebastian; Ortiz, Xoana P.; Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection; Elsevier; Journal of Virological Methods; 199; 1-2014; 1-100166-0934CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0166093413005181info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jviromet.2013.12.016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:01:15Zoai:ri.conicet.gov.ar:11336/33657instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:01:16.087CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
title Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
spellingShingle Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
Gismondi, Maria Ines
Artificial Micrornas
Antiviral
Fmdv
Accessibility
Rna Structure
title_short Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
title_full Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
title_fullStr Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
title_full_unstemmed Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
title_sort Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection
dc.creator.none.fl_str_mv Gismondi, Maria Ines
Ortiz, Xoana P.
Currá, Anabella Paola
Asurmendi, Sebastian
Taboga, Oscar Alberto
author Gismondi, Maria Ines
author_facet Gismondi, Maria Ines
Ortiz, Xoana P.
Currá, Anabella Paola
Asurmendi, Sebastian
Taboga, Oscar Alberto
author_role author
author2 Ortiz, Xoana P.
Currá, Anabella Paola
Asurmendi, Sebastian
Taboga, Oscar Alberto
author2_role author
author
author
author
dc.subject.none.fl_str_mv Artificial Micrornas
Antiviral
Fmdv
Accessibility
Rna Structure
topic Artificial Micrornas
Antiviral
Fmdv
Accessibility
Rna Structure
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/4.4
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv RNA interference (RNAi) appears as a promising strategy to control virus replication. While the antiviral power of short-hairpin RNAs or small-interfering RNAs against FMDV has been demonstrated widely, safer RNAi effectors such as artificial microRNAs (amiRs) have not been evaluated extensively. In this work, transgenic monoclonal cell lines constitutively expressing different amiRs targeting FMDV 3D-coding region or 3´UTR were established. Certain cell lines showed an effective, sequence-specific amiR-mediated silencing activity that was accomplished by degradation of the target mRNA, as demonstrated in co-transfection experiments of reporter genes fused to FMDV target sequences. However, FMDV replication in these amiR-expressing cells was affected barely. Experiments aimed at elucidating the cause of RNAi failure demonstrated limited accessibility of the targeted region in the molecular environment of the viral RNA. Since RNAi is mediated by large-dimension silencing complexes containing the siRNA and not simply by a linear oligonucleotide, we propose that target selection should consider not only the local RNA structure but also the global conformation of target RNA.
Fil: Gismondi, Maria Ines. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ortiz, Xoana P.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Currá, Anabella Paola. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Asurmendi, Sebastian. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Taboga, Oscar Alberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description RNA interference (RNAi) appears as a promising strategy to control virus replication. While the antiviral power of short-hairpin RNAs or small-interfering RNAs against FMDV has been demonstrated widely, safer RNAi effectors such as artificial microRNAs (amiRs) have not been evaluated extensively. In this work, transgenic monoclonal cell lines constitutively expressing different amiRs targeting FMDV 3D-coding region or 3´UTR were established. Certain cell lines showed an effective, sequence-specific amiR-mediated silencing activity that was accomplished by degradation of the target mRNA, as demonstrated in co-transfection experiments of reporter genes fused to FMDV target sequences. However, FMDV replication in these amiR-expressing cells was affected barely. Experiments aimed at elucidating the cause of RNAi failure demonstrated limited accessibility of the targeted region in the molecular environment of the viral RNA. Since RNAi is mediated by large-dimension silencing complexes containing the siRNA and not simply by a linear oligonucleotide, we propose that target selection should consider not only the local RNA structure but also the global conformation of target RNA.
publishDate 2014
dc.date.none.fl_str_mv 2014-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/33657
Taboga, Oscar Alberto; Currá, Anabella Paola; Gismondi, Maria Ines; Asurmendi, Sebastian; Ortiz, Xoana P.; Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection; Elsevier; Journal of Virological Methods; 199; 1-2014; 1-10
0166-0934
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33657
identifier_str_mv Taboga, Oscar Alberto; Currá, Anabella Paola; Gismondi, Maria Ines; Asurmendi, Sebastian; Ortiz, Xoana P.; Artificial microRNAs as antiviral strategy to FMDV: structural implications of target selection; Elsevier; Journal of Virological Methods; 199; 1-2014; 1-10
0166-0934
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0166093413005181
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jviromet.2013.12.016
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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