Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA

Autores
Rivera, Rodrigo; Valdebenito, Cristian Esteban; Roman, Ernesto Andres; Baez, Mauricio
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Temperature is one of the most fundamental physical variables governing RNA folding, yet its effects at low temperature remain incompletely understood. Recent single-molecule studies indicate that lowering temperature below a characteristic threshold (~ 20 °C) alters the folding pathways and promotes the population of non-native intermediates, including non-native conformations not predicted by standard secondary-structure models. Here, we combine temperature-controlled optical tweezers with computational free-energy landscape analysis to examine how the architecture of the HIV-1 TAR RNA hairpin modulates folding in this low-temperature regime. We show that decreasing temperature stabilizes the native hairpin but, below ~ 20 °C, promotes two distinct classes of misfolded intermediates dependent on the presence of the conserved three-nucleotide bulge. Together, the experimental data and the free-energy landscape analysis indicate that the presence of the bulge, not the loop, underlies the emergence of these low-temperature misfolded intermediates, accounting for their distinct mechanical signatures compared to those reported for RNA hairpins with a long loop.
Fil: Rivera, Rodrigo. Universidad de Chile.; Chile
Fil: Valdebenito, Cristian Esteban. Universidad de Chile.; Chile
Fil: Roman, Ernesto Andres. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Baez, Mauricio. Universidad de Chile.; Chile
Materia
molecula-unica
RNA
Pinzas-opticas
Temperatura
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/290155
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNARivera, RodrigoValdebenito, Cristian EstebanRoman, Ernesto AndresBaez, Mauriciomolecula-unicaRNAPinzas-opticasTemperaturahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Temperature is one of the most fundamental physical variables governing RNA folding, yet its effects at low temperature remain incompletely understood. Recent single-molecule studies indicate that lowering temperature below a characteristic threshold (~ 20 °C) alters the folding pathways and promotes the population of non-native intermediates, including non-native conformations not predicted by standard secondary-structure models. Here, we combine temperature-controlled optical tweezers with computational free-energy landscape analysis to examine how the architecture of the HIV-1 TAR RNA hairpin modulates folding in this low-temperature regime. We show that decreasing temperature stabilizes the native hairpin but, below ~ 20 °C, promotes two distinct classes of misfolded intermediates dependent on the presence of the conserved three-nucleotide bulge. Together, the experimental data and the free-energy landscape analysis indicate that the presence of the bulge, not the loop, underlies the emergence of these low-temperature misfolded intermediates, accounting for their distinct mechanical signatures compared to those reported for RNA hairpins with a long loop.Fil: Rivera, Rodrigo. Universidad de Chile.; ChileFil: Valdebenito, Cristian Esteban. Universidad de Chile.; ChileFil: Roman, Ernesto Andres. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Baez, Mauricio. Universidad de Chile.; ChileNature2026-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/290155Rivera, Rodrigo; Valdebenito, Cristian Esteban; Roman, Ernesto Andres; Baez, Mauricio; Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA; Nature; Scientific Reports; 16; 1; 4-2026; 1-302045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-026-49876-3info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-026-49876-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:51:36Zoai:ri.conicet.gov.ar:11336/290155instacron: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:34982026-08-25 14:51:36.355CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
title Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
spellingShingle Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
Rivera, Rodrigo
molecula-unica
RNA
Pinzas-opticas
Temperatura
title_short Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
title_full Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
title_fullStr Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
title_full_unstemmed Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
title_sort Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA
dc.creator.none.fl_str_mv Rivera, Rodrigo
Valdebenito, Cristian Esteban
Roman, Ernesto Andres
Baez, Mauricio
author Rivera, Rodrigo
author_facet Rivera, Rodrigo
Valdebenito, Cristian Esteban
Roman, Ernesto Andres
Baez, Mauricio
author_role author
author2 Valdebenito, Cristian Esteban
Roman, Ernesto Andres
Baez, Mauricio
author2_role author
author
author
dc.subject.none.fl_str_mv molecula-unica
RNA
Pinzas-opticas
Temperatura
topic molecula-unica
RNA
Pinzas-opticas
Temperatura
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Temperature is one of the most fundamental physical variables governing RNA folding, yet its effects at low temperature remain incompletely understood. Recent single-molecule studies indicate that lowering temperature below a characteristic threshold (~ 20 °C) alters the folding pathways and promotes the population of non-native intermediates, including non-native conformations not predicted by standard secondary-structure models. Here, we combine temperature-controlled optical tweezers with computational free-energy landscape analysis to examine how the architecture of the HIV-1 TAR RNA hairpin modulates folding in this low-temperature regime. We show that decreasing temperature stabilizes the native hairpin but, below ~ 20 °C, promotes two distinct classes of misfolded intermediates dependent on the presence of the conserved three-nucleotide bulge. Together, the experimental data and the free-energy landscape analysis indicate that the presence of the bulge, not the loop, underlies the emergence of these low-temperature misfolded intermediates, accounting for their distinct mechanical signatures compared to those reported for RNA hairpins with a long loop.
Fil: Rivera, Rodrigo. Universidad de Chile.; Chile
Fil: Valdebenito, Cristian Esteban. Universidad de Chile.; Chile
Fil: Roman, Ernesto Andres. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Baez, Mauricio. Universidad de Chile.; Chile
description Temperature is one of the most fundamental physical variables governing RNA folding, yet its effects at low temperature remain incompletely understood. Recent single-molecule studies indicate that lowering temperature below a characteristic threshold (~ 20 °C) alters the folding pathways and promotes the population of non-native intermediates, including non-native conformations not predicted by standard secondary-structure models. Here, we combine temperature-controlled optical tweezers with computational free-energy landscape analysis to examine how the architecture of the HIV-1 TAR RNA hairpin modulates folding in this low-temperature regime. We show that decreasing temperature stabilizes the native hairpin but, below ~ 20 °C, promotes two distinct classes of misfolded intermediates dependent on the presence of the conserved three-nucleotide bulge. Together, the experimental data and the free-energy landscape analysis indicate that the presence of the bulge, not the loop, underlies the emergence of these low-temperature misfolded intermediates, accounting for their distinct mechanical signatures compared to those reported for RNA hairpins with a long loop.
publishDate 2026
dc.date.none.fl_str_mv 2026-04
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/11336/290155
Rivera, Rodrigo; Valdebenito, Cristian Esteban; Roman, Ernesto Andres; Baez, Mauricio; Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA; Nature; Scientific Reports; 16; 1; 4-2026; 1-30
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/290155
identifier_str_mv Rivera, Rodrigo; Valdebenito, Cristian Esteban; Roman, Ernesto Andres; Baez, Mauricio; Single-molecule analysis reveals low-temperature misfolding in HIV-1 TAR RNA; Nature; Scientific Reports; 16; 1; 4-2026; 1-30
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-026-49876-3
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-026-49876-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
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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