The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity

Autores
Sabalette, Karina Belén; Romaniuk, María Albertina; Noé, Griselda; Cassola, Alejandro Carlos; Campo, Vanina Andrea; de Gaudenzi, Javier Gerardo
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The regulation of transcription in trypanosomes is unusual. To modulate protein synthesis during their complex developmental stages, these unicellular microorganisms rely largely on post-transcriptional gene expression pathways. These pathways include a plethora of RNA-binding proteins (RBPs) that modulate all steps of the mRNA life cycle in trypanosomes and help organize transcriptomes into clusters of post-transcriptional regulons. The aim of this work was to characterize an RNA regulon comprising numerous transcripts of trypomastigote-associated cell-surface glycoproteins that are preferentially expressed in the infective stages of the human parasite Trypanosoma cruzi. In vitro and in vivo RNA-binding assays disclosed that these glycoprotein mRNAs are targeted by the small trypanosomatid-exclusive RBP in T. cruzi, U-rich RBP 1 (TcUBP1). Overexpression of a GFP-tagged TcUBP1 in replicative parasites resulted in >10 times up-regulated expression of transcripts encoding surface proteins and in changes in their subcellular localization from the posterior region to the perinuclear region of the cytoplasm, as is typically observed in the infective parasite stages. Moreover, RT–quantitative PCR analysis of actively translated mRNAs by sucrose cushion fractionation revealed an increased abundance of these target transcripts in the polysome fraction of TcUBP1-induced samples. Because these surface proteins are involved in cell adherence or invasion during host infection, we also carried out in vitro infections with TcUBP1-transgenic trypomastigotes and observed that TcUBP1 overexpression significantly increases parasite infectivity. Our findings provide evidence for a role of TcUBP1 in trypomastigote stage-specific gene regulation important for T. cruzi virulence.
Fil: Sabalette, Karina Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Noé, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Cassola, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Campo, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: de Gaudenzi, Javier Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Materia
RNA
TRYPANOSOMES
GENE REGULATION
VIRULENCE
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:11336/112202
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/112202
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivitySabalette, Karina BelénRomaniuk, María AlbertinaNoé, GriseldaCassola, Alejandro CarlosCampo, Vanina Andreade Gaudenzi, Javier GerardoRNATRYPANOSOMESGENE REGULATIONVIRULENCEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The regulation of transcription in trypanosomes is unusual. To modulate protein synthesis during their complex developmental stages, these unicellular microorganisms rely largely on post-transcriptional gene expression pathways. These pathways include a plethora of RNA-binding proteins (RBPs) that modulate all steps of the mRNA life cycle in trypanosomes and help organize transcriptomes into clusters of post-transcriptional regulons. The aim of this work was to characterize an RNA regulon comprising numerous transcripts of trypomastigote-associated cell-surface glycoproteins that are preferentially expressed in the infective stages of the human parasite Trypanosoma cruzi. In vitro and in vivo RNA-binding assays disclosed that these glycoprotein mRNAs are targeted by the small trypanosomatid-exclusive RBP in T. cruzi, U-rich RBP 1 (TcUBP1). Overexpression of a GFP-tagged TcUBP1 in replicative parasites resulted in >10 times up-regulated expression of transcripts encoding surface proteins and in changes in their subcellular localization from the posterior region to the perinuclear region of the cytoplasm, as is typically observed in the infective parasite stages. Moreover, RT–quantitative PCR analysis of actively translated mRNAs by sucrose cushion fractionation revealed an increased abundance of these target transcripts in the polysome fraction of TcUBP1-induced samples. Because these surface proteins are involved in cell adherence or invasion during host infection, we also carried out in vitro infections with TcUBP1-transgenic trypomastigotes and observed that TcUBP1 overexpression significantly increases parasite infectivity. Our findings provide evidence for a role of TcUBP1 in trypomastigote stage-specific gene regulation important for T. cruzi virulence.Fil: Sabalette, Karina Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Noé, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Cassola, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Campo, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: de Gaudenzi, Javier Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaAmerican Society for Biochemistry and Molecular Biology2019-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112202Sabalette, Karina Belén; Romaniuk, María Albertina; Noé, Griselda; Cassola, Alejandro Carlos; Campo, Vanina Andrea; et al.; The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 294; 26; 6-2019; 10349-103640021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/lookup/doi/10.1074/jbc.RA118.007123info:eu-repo/semantics/altIdentifier/doi/10.1074/JBC.RA118.007123info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:05Zoai:ri.conicet.gov.ar:11336/112202instacron: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:34982025-09-03 10:08:06.127CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
title The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
spellingShingle The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
Sabalette, Karina Belén
RNA
TRYPANOSOMES
GENE REGULATION
VIRULENCE
title_short The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
title_full The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
title_fullStr The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
title_full_unstemmed The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
title_sort The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity
dc.creator.none.fl_str_mv Sabalette, Karina Belén
Romaniuk, María Albertina
Noé, Griselda
Cassola, Alejandro Carlos
Campo, Vanina Andrea
de Gaudenzi, Javier Gerardo
author Sabalette, Karina Belén
author_facet Sabalette, Karina Belén
Romaniuk, María Albertina
Noé, Griselda
Cassola, Alejandro Carlos
Campo, Vanina Andrea
de Gaudenzi, Javier Gerardo
author_role author
author2 Romaniuk, María Albertina
Noé, Griselda
Cassola, Alejandro Carlos
Campo, Vanina Andrea
de Gaudenzi, Javier Gerardo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv RNA
TRYPANOSOMES
GENE REGULATION
VIRULENCE
topic RNA
TRYPANOSOMES
GENE REGULATION
VIRULENCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The regulation of transcription in trypanosomes is unusual. To modulate protein synthesis during their complex developmental stages, these unicellular microorganisms rely largely on post-transcriptional gene expression pathways. These pathways include a plethora of RNA-binding proteins (RBPs) that modulate all steps of the mRNA life cycle in trypanosomes and help organize transcriptomes into clusters of post-transcriptional regulons. The aim of this work was to characterize an RNA regulon comprising numerous transcripts of trypomastigote-associated cell-surface glycoproteins that are preferentially expressed in the infective stages of the human parasite Trypanosoma cruzi. In vitro and in vivo RNA-binding assays disclosed that these glycoprotein mRNAs are targeted by the small trypanosomatid-exclusive RBP in T. cruzi, U-rich RBP 1 (TcUBP1). Overexpression of a GFP-tagged TcUBP1 in replicative parasites resulted in >10 times up-regulated expression of transcripts encoding surface proteins and in changes in their subcellular localization from the posterior region to the perinuclear region of the cytoplasm, as is typically observed in the infective parasite stages. Moreover, RT–quantitative PCR analysis of actively translated mRNAs by sucrose cushion fractionation revealed an increased abundance of these target transcripts in the polysome fraction of TcUBP1-induced samples. Because these surface proteins are involved in cell adherence or invasion during host infection, we also carried out in vitro infections with TcUBP1-transgenic trypomastigotes and observed that TcUBP1 overexpression significantly increases parasite infectivity. Our findings provide evidence for a role of TcUBP1 in trypomastigote stage-specific gene regulation important for T. cruzi virulence.
Fil: Sabalette, Karina Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Noé, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Cassola, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Campo, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: de Gaudenzi, Javier Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
description The regulation of transcription in trypanosomes is unusual. To modulate protein synthesis during their complex developmental stages, these unicellular microorganisms rely largely on post-transcriptional gene expression pathways. These pathways include a plethora of RNA-binding proteins (RBPs) that modulate all steps of the mRNA life cycle in trypanosomes and help organize transcriptomes into clusters of post-transcriptional regulons. The aim of this work was to characterize an RNA regulon comprising numerous transcripts of trypomastigote-associated cell-surface glycoproteins that are preferentially expressed in the infective stages of the human parasite Trypanosoma cruzi. In vitro and in vivo RNA-binding assays disclosed that these glycoprotein mRNAs are targeted by the small trypanosomatid-exclusive RBP in T. cruzi, U-rich RBP 1 (TcUBP1). Overexpression of a GFP-tagged TcUBP1 in replicative parasites resulted in >10 times up-regulated expression of transcripts encoding surface proteins and in changes in their subcellular localization from the posterior region to the perinuclear region of the cytoplasm, as is typically observed in the infective parasite stages. Moreover, RT–quantitative PCR analysis of actively translated mRNAs by sucrose cushion fractionation revealed an increased abundance of these target transcripts in the polysome fraction of TcUBP1-induced samples. Because these surface proteins are involved in cell adherence or invasion during host infection, we also carried out in vitro infections with TcUBP1-transgenic trypomastigotes and observed that TcUBP1 overexpression significantly increases parasite infectivity. Our findings provide evidence for a role of TcUBP1 in trypomastigote stage-specific gene regulation important for T. cruzi virulence.
publishDate 2019
dc.date.none.fl_str_mv 2019-06
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/11336/112202
Sabalette, Karina Belén; Romaniuk, María Albertina; Noé, Griselda; Cassola, Alejandro Carlos; Campo, Vanina Andrea; et al.; The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 294; 26; 6-2019; 10349-10364
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112202
identifier_str_mv Sabalette, Karina Belén; Romaniuk, María Albertina; Noé, Griselda; Cassola, Alejandro Carlos; Campo, Vanina Andrea; et al.; The RNA-binding protein TcUBP1 up-regulates an RNA regulon for a cell surface–associated Trypanosoma cruzi glycoprotein and promotes parasite infectivity; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 294; 26; 6-2019; 10349-10364
0021-9258
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.jbc.org/lookup/doi/10.1074/jbc.RA118.007123
info:eu-repo/semantics/altIdentifier/doi/10.1074/JBC.RA118.007123
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
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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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