Double-stranded RNA bending by AU-tract sequences
Sequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. However, in contrast to dsDNA, sequence-dependent structural features of dsRNA have received little...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/711174 |
| Acceso en línea: | http://hdl.handle.net/10486/711174 https://dx.doi.org/10.1093/nar/gkaa1128 |
| Access Level: | acceso abierto |
| Palabra clave: | Adenine DNA Microscopy, Atomic Force Molecular Dynamics Simulation Nucleic Acid Conformation Nucleotide Motifs RNA, Double-Stranded Uracil Física |
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Double-stranded RNA bending by AU-tract sequencesMarín-González, AlbertoAicart-Ramos, ClaraMarin-Baquero, MikelMartín González, AlejandroVilhena, J.G.Moreno-Herrero, FernandoSuomalainen, MaaritKannan, AbhilashGreber, Urs F.Pérez Pérez, RubénAdenineDNAMicroscopy, Atomic ForceMolecular Dynamics SimulationNucleic Acid ConformationNucleotide MotifsRNA, Double-StrandedUracilFísicaSequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. However, in contrast to dsDNA, sequence-dependent structural features of dsRNA have received little attention. In this work, we demonstrate that the nucleotide sequence can induce a bend in a canonical Watson-Crick base-paired dsRNA helix. Using all-atom molecular dynamics simulations, we identified a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that strongly bend the RNA double-helix. This finding was experimentally validated using atomic force microscopy imaging of dsRNA molecules designed to display macroscopic curvature via repetitions of phased AU-tract motifs. At the atomic level, this novel phenomenon originates from a localized compression of the dsRNA major groove and a large propeller twist at the position of the AU-tract. Moreover, the magnitude of the bending can be modulated by changing the length of the AU-tract. Altogether, our results demonstrate the possibility of modifying the dsRNA curvature by means of its nucleotide sequence, which may be exploited in the emerging field of RNA nanotechnology and might also constitute a natural mechanism for proteins to achieve recognition of specific dsRNA sequencesSpanish MINECO [MAT2017-83273-R (AEI/FEDER, UE) to R.P., BFU2017-83794-P (AEI/FEDER, UE to F.M.-H.) and Comunidad de Madrid (Tec4Bio - S2018/NMT-4443 and NanoBioCancer - Y2018/BIO-4747 to F.M.-H.]; R.P. acknowledges support from the Spanish Ministry of Science and Innovation, through the 'María de Maeztu' Programme for Units of Excellence in R&D [CEX2018-000805-M]; F.M.-H. acknowledges support from European Research Council (ERC) under the European Union Horizon 2020 research and innovation [681299]; J. G. V. acknowledges funding from a Marie Sklodowska-Curie Fellowship within the Horizons 2020 framework (DLV-795286) and the Swiss National Science Foundation (grant number CRSK-2 190731/1). Alberto M.-G. acknowledges support from the International PhD Program of 'La Caixa-Severo Ochoa' as a recipient of a PhD fellowship; U.F.G. acknowledges support from the Swiss National Science Foundation [31003A 179256/1]; Alejandro M.-G. and MM-B acknowledge support from the Spanish Ministry of Competitiveness and Industry as a recipients of a FPI fellowship [REFs BES-2015-071244, PRE2018-083464, respectively]. Funding for open access charge: European Research Council (ERC) [681299]. Conflict of interest statement. None declared.Oxford University PressDepartamento de Física Teórica de la Materia CondensadaFacultad de Ciencias20202020-12-16research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/711174https://dx.doi.org/10.1093/nar/gkaa1128reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7111742026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Double-stranded RNA bending by AU-tract sequences |
| title |
Double-stranded RNA bending by AU-tract sequences |
| spellingShingle |
Double-stranded RNA bending by AU-tract sequences Marín-González, Alberto Adenine DNA Microscopy, Atomic Force Molecular Dynamics Simulation Nucleic Acid Conformation Nucleotide Motifs RNA, Double-Stranded Uracil Física |
| title_short |
Double-stranded RNA bending by AU-tract sequences |
| title_full |
Double-stranded RNA bending by AU-tract sequences |
| title_fullStr |
Double-stranded RNA bending by AU-tract sequences |
| title_full_unstemmed |
Double-stranded RNA bending by AU-tract sequences |
| title_sort |
Double-stranded RNA bending by AU-tract sequences |
| dc.creator.none.fl_str_mv |
Marín-González, Alberto Aicart-Ramos, Clara Marin-Baquero, Mikel Martín González, Alejandro Vilhena, J.G. Moreno-Herrero, Fernando Suomalainen, Maarit Kannan, Abhilash Greber, Urs F. Pérez Pérez, Rubén |
| author |
Marín-González, Alberto |
| author_facet |
Marín-González, Alberto Aicart-Ramos, Clara Marin-Baquero, Mikel Martín González, Alejandro Vilhena, J.G. Moreno-Herrero, Fernando Suomalainen, Maarit Kannan, Abhilash Greber, Urs F. Pérez Pérez, Rubén |
| author_role |
author |
| author2 |
Aicart-Ramos, Clara Marin-Baquero, Mikel Martín González, Alejandro Vilhena, J.G. Moreno-Herrero, Fernando Suomalainen, Maarit Kannan, Abhilash Greber, Urs F. Pérez Pérez, Rubén |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Física Teórica de la Materia Condensada Facultad de Ciencias |
| dc.subject.none.fl_str_mv |
Adenine DNA Microscopy, Atomic Force Molecular Dynamics Simulation Nucleic Acid Conformation Nucleotide Motifs RNA, Double-Stranded Uracil Física |
| topic |
Adenine DNA Microscopy, Atomic Force Molecular Dynamics Simulation Nucleic Acid Conformation Nucleotide Motifs RNA, Double-Stranded Uracil Física |
| description |
Sequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. However, in contrast to dsDNA, sequence-dependent structural features of dsRNA have received little attention. In this work, we demonstrate that the nucleotide sequence can induce a bend in a canonical Watson-Crick base-paired dsRNA helix. Using all-atom molecular dynamics simulations, we identified a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that strongly bend the RNA double-helix. This finding was experimentally validated using atomic force microscopy imaging of dsRNA molecules designed to display macroscopic curvature via repetitions of phased AU-tract motifs. At the atomic level, this novel phenomenon originates from a localized compression of the dsRNA major groove and a large propeller twist at the position of the AU-tract. Moreover, the magnitude of the bending can be modulated by changing the length of the AU-tract. Altogether, our results demonstrate the possibility of modifying the dsRNA curvature by means of its nucleotide sequence, which may be exploited in the emerging field of RNA nanotechnology and might also constitute a natural mechanism for proteins to achieve recognition of specific dsRNA sequences |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-12-16 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/711174 https://dx.doi.org/10.1093/nar/gkaa1128 |
| url |
http://hdl.handle.net/10486/711174 https://dx.doi.org/10.1093/nar/gkaa1128 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Oxford University Press |
| publisher.none.fl_str_mv |
Oxford University Press |
| dc.source.none.fl_str_mv |
reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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