Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors

Autores
Foscaldi, Sabrina Andrea; D'antuono, Alejandra Lorena; Noval, María Gabriela; de Prat Gay, Gonzalo; Scolaro, Luis Alberto; Lopez, Nora Mabel
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mammarenaviruses are enveloped viruses with a bisegmented negativestranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5' untranslated region (UTR) and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5' and/or 3' UTR were evaluated in a cellbased translation assay. We found that the presence of the cap structure at the 5' end dramatically increases translation efficiency and that the viral 5' UTR comprises stimulatory signals while the 3' UTR,specifically the presence of a terminal C+G-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5' UTR and a negative modulatory element in the 3' UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism.
Fil: Foscaldi, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: D'antuono, Alejandra Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Noval, María Gabriela. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Scolaro, Luis Alberto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Materia
Arenavirus
Mrna
Translation
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:11336/40344
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/40344
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factorsFoscaldi, Sabrina AndreaD'antuono, Alejandra LorenaNoval, María Gabrielade Prat Gay, GonzaloScolaro, Luis AlbertoLopez, Nora MabelArenavirusMrnaTranslationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mammarenaviruses are enveloped viruses with a bisegmented negativestranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5' untranslated region (UTR) and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5' and/or 3' UTR were evaluated in a cellbased translation assay. We found that the presence of the cap structure at the 5' end dramatically increases translation efficiency and that the viral 5' UTR comprises stimulatory signals while the 3' UTR,specifically the presence of a terminal C+G-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5' UTR and a negative modulatory element in the 3' UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism.Fil: Foscaldi, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; ArgentinaFil: D'antuono, Alejandra Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; ArgentinaFil: Noval, María Gabriela. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scolaro, Luis Alberto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; ArgentinaAmerican Society for Microbiology2017-07info: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/11336/40344Foscaldi, Sabrina Andrea; D'antuono, Alejandra Lorena; Noval, María Gabriela; de Prat Gay, Gonzalo; Scolaro, Luis Alberto; et al.; Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors; American Society for Microbiology; Journal of Virology; 91; 14; 7-2017; 1-15; e00084-170022-538XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/JVI.00084-17info:eu-repo/semantics/altIdentifier/url/http://jvi.asm.org/content/91/14/e00084-17info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:05Zoai:ri.conicet.gov.ar:11336/40344instacron: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:34982025-09-29 09:34:05.721CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
spellingShingle Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
Foscaldi, Sabrina Andrea
Arenavirus
Mrna
Translation
title_short Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_full Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_fullStr Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_full_unstemmed Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_sort Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
dc.creator.none.fl_str_mv Foscaldi, Sabrina Andrea
D'antuono, Alejandra Lorena
Noval, María Gabriela
de Prat Gay, Gonzalo
Scolaro, Luis Alberto
Lopez, Nora Mabel
author Foscaldi, Sabrina Andrea
author_facet Foscaldi, Sabrina Andrea
D'antuono, Alejandra Lorena
Noval, María Gabriela
de Prat Gay, Gonzalo
Scolaro, Luis Alberto
Lopez, Nora Mabel
author_role author
author2 D'antuono, Alejandra Lorena
Noval, María Gabriela
de Prat Gay, Gonzalo
Scolaro, Luis Alberto
Lopez, Nora Mabel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Arenavirus
Mrna
Translation
topic Arenavirus
Mrna
Translation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mammarenaviruses are enveloped viruses with a bisegmented negativestranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5' untranslated region (UTR) and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5' and/or 3' UTR were evaluated in a cellbased translation assay. We found that the presence of the cap structure at the 5' end dramatically increases translation efficiency and that the viral 5' UTR comprises stimulatory signals while the 3' UTR,specifically the presence of a terminal C+G-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5' UTR and a negative modulatory element in the 3' UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism.
Fil: Foscaldi, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: D'antuono, Alejandra Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Noval, María Gabriela. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Scolaro, Luis Alberto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
description Mammarenaviruses are enveloped viruses with a bisegmented negativestranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5' untranslated region (UTR) and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5' and/or 3' UTR were evaluated in a cellbased translation assay. We found that the presence of the cap structure at the 5' end dramatically increases translation efficiency and that the viral 5' UTR comprises stimulatory signals while the 3' UTR,specifically the presence of a terminal C+G-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5' UTR and a negative modulatory element in the 3' UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism.
publishDate 2017
dc.date.none.fl_str_mv 2017-07
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/11336/40344
Foscaldi, Sabrina Andrea; D'antuono, Alejandra Lorena; Noval, María Gabriela; de Prat Gay, Gonzalo; Scolaro, Luis Alberto; et al.; Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors; American Society for Microbiology; Journal of Virology; 91; 14; 7-2017; 1-15; e00084-17
0022-538X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/40344
identifier_str_mv Foscaldi, Sabrina Andrea; D'antuono, Alejandra Lorena; Noval, María Gabriela; de Prat Gay, Gonzalo; Scolaro, Luis Alberto; et al.; Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors; American Society for Microbiology; Journal of Virology; 91; 14; 7-2017; 1-15; e00084-17
0022-538X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/JVI.00084-17
info:eu-repo/semantics/altIdentifier/url/http://jvi.asm.org/content/91/14/e00084-17
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
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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 13.070432

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