Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units

The understanding of the mechanisms behind nucleotide recognition by Argonaute 2, core protein of the RNA-induced silencing complex, is a key aspect in the optimization of small interfering RNAs (siRNAs) activity. To date, great efforts have been focused on the modification of certain regions of siR...

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Autores: Alagia, Adele, Terrazas Martínez, Montserrat, Eritja i Casadellà, Ramon
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/179404
Acceso en línea:https://hdl.handle.net/2445/179404
Access Level:acceso abierto
Palabra clave:RNA
Regulació genètica
Àcids nucleics
Genetic regulation
Nucleic acids
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spelling Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) unitsAlagia, AdeleTerrazas Martínez, MontserratEritja i Casadellà, RamonRNARegulació genèticaÀcids nucleicsRNAGenetic regulationNucleic acidsThe understanding of the mechanisms behind nucleotide recognition by Argonaute 2, core protein of the RNA-induced silencing complex, is a key aspect in the optimization of small interfering RNAs (siRNAs) activity. To date, great efforts have been focused on the modification of certain regions of siRNA, such as the 3'/5'-termini and the seed region. Only a few reports have described the roles of central positions flanking the cleavage site during the silence process. In this study, we investigate the potential correlations between the thermodynamic and silencing properties of siRNA molecules carrying, at internal positions, an acyclic L-threoninol nucleic acid (aTNA) modification. Depending on position, the silencing is weakened or impaired. Furthermore, we evaluate the contribution of mismatches facing either a natural nucleotide or an aTNA modification to the siRNA potency. The position 11 of the antisense strand is more permissive to mismatches and aTNA modification, in respect to the position 10. Additionally, comparing the ON-/OFF-target silencing of central mismatched siRNAs with 5'-terminal modified siRNA, we concluded: (i) central perturbation of duplex pairing features weights more on potency rather than silencing asymmetry; (ii) complete bias for the ON-target silencing can be achieved with single L-threoninol modification near the 5'-end of the sense strand.MDPI2021202120152021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/179404Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/molecules20057602Molecules, 2015, vol. 20, num. 5, p. 7602-7619https://doi.org/10.3390/molecules20057602info:eu-repo/grantAgreement/EC/FP7/262943cc-by (c) Alagia, Adele et al., 2015https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1794042026-05-29T05:05:01Z
dc.title.none.fl_str_mv Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
title Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
spellingShingle Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
Alagia, Adele
RNA
Regulació genètica
Àcids nucleics
RNA
Genetic regulation
Nucleic acids
title_short Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
title_full Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
title_fullStr Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
title_full_unstemmed Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
title_sort Modulation of the RNA interference activity using mismatched siRNAs and acyclic threoninol nucleic acids (aTNA) units
dc.creator.none.fl_str_mv Alagia, Adele
Terrazas Martínez, Montserrat
Eritja i Casadellà, Ramon
author Alagia, Adele
author_facet Alagia, Adele
Terrazas Martínez, Montserrat
Eritja i Casadellà, Ramon
author_role author
author2 Terrazas Martínez, Montserrat
Eritja i Casadellà, Ramon
author2_role author
author
dc.subject.none.fl_str_mv RNA
Regulació genètica
Àcids nucleics
RNA
Genetic regulation
Nucleic acids
topic RNA
Regulació genètica
Àcids nucleics
RNA
Genetic regulation
Nucleic acids
description The understanding of the mechanisms behind nucleotide recognition by Argonaute 2, core protein of the RNA-induced silencing complex, is a key aspect in the optimization of small interfering RNAs (siRNAs) activity. To date, great efforts have been focused on the modification of certain regions of siRNA, such as the 3'/5'-termini and the seed region. Only a few reports have described the roles of central positions flanking the cleavage site during the silence process. In this study, we investigate the potential correlations between the thermodynamic and silencing properties of siRNA molecules carrying, at internal positions, an acyclic L-threoninol nucleic acid (aTNA) modification. Depending on position, the silencing is weakened or impaired. Furthermore, we evaluate the contribution of mismatches facing either a natural nucleotide or an aTNA modification to the siRNA potency. The position 11 of the antisense strand is more permissive to mismatches and aTNA modification, in respect to the position 10. Additionally, comparing the ON-/OFF-target silencing of central mismatched siRNAs with 5'-terminal modified siRNA, we concluded: (i) central perturbation of duplex pairing features weights more on potency rather than silencing asymmetry; (ii) complete bias for the ON-target silencing can be achieved with single L-threoninol modification near the 5'-end of the sense strand.
publishDate 2015
dc.date.none.fl_str_mv 2015
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/179404
url https://hdl.handle.net/2445/179404
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/molecules20057602
Molecules, 2015, vol. 20, num. 5, p. 7602-7619
https://doi.org/10.3390/molecules20057602
info:eu-repo/grantAgreement/EC/FP7/262943
dc.rights.none.fl_str_mv cc-by (c) Alagia, Adele et al., 2015
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Alagia, Adele et al., 2015
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414952671903744
score 15,811543

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