Dengue virus targets RBM10 deregulating host cell splicing and innate immune response
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/53279 |
Resumo: | © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
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Dengue virus targets RBM10 deregulating host cell splicing and innate immune response© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comRNA-seq experiments previously performed by our laboratories showed enrichment in intronic sequences and alterations in alternative splicing in dengue-infected human cells. The transcript of the SAT1 gene, of well-known antiviral action, displayed higher inclusion of exon 4 in infected cells, leading to an mRNA isoform that is degraded by non-sense mediated decay. SAT1 is a spermidine/spermine acetyl-transferase enzyme that decreases the reservoir of cellular polyamines, limiting viral replication. Delving into the molecular mechanism underlying SAT1 pre-mRNA splicing changes upon viral infection, we observed lower protein levels of RBM10, a splicing factor responsible for SAT1 exon 4 skipping. We found that the dengue polymerase NS5 interacts with RBM10 and its sole expression triggers RBM10 proteasome-mediated degradation. RBM10 over-expression in infected cells prevents SAT1 splicing changes and limits viral replication, while its knock-down enhances the splicing switch and also benefits viral replication, revealing an anti-viral role for RBM10. Consistently, RBM10 depletion attenuates expression of interferon and pro-inflammatory cytokines. In particular, we found that RBM10 interacts with viral RNA and RIG-I, and even promotes the ubiquitination of the latter, a crucial step for its activation. We propose RBM10 fulfills diverse pro-inflammatory, anti-viral tasks, besides its well-documented role in splicing regulation of apoptotic genes.Agencia Nacional de Promoción Científica y Tecnológica de Argentina (ANPCyT) [2014-2888, 2015-1731, 2017-0111 to A.S. and 2015-2555, 2017-1717 to A.V.G.]; Universidad de Buenos Aires, Argentina (UBACyT) [20020170100045BA to A.S.]; NIH (NIAID) [R01.AI095175 to A.V.G.]; Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET) [PIP 11220170100171CO to C.C.G]; B.P. has been a postdoctoral fellow from CONICET from 2017 to 2019 and is currently a postdoctoral fellow at the Institute of Cell Biology in the University of Bern, Switzerland; L.B. and M.E.G.S. are recipients of doctoral fellowships from CONICET; M.F.T. is a doctoral fellowship recipient from ANPCyT; N.G. has been an undergraduate fellowship recipient from the University of Buenos Aires (2018–2020); P.M. has been a doctoral fellow from CONICET (2015–2019) and is currently a postdoctoral fellow supported by H2020-Marie Sklodowska-Curie Research and Innovation Staff Exchanges [734825-LysoMod]; R.V.D. has been a visiting post-doctoral fellow at the Srebrow lab from IMM (Lisbon, Portugal) supported by the same program. A.S., A.V.G., C.C.G., N.G.I. and L.G.G. are career investigators from CONICET.Oxford University PressRepositório da Universidade de LisboaSrebrow, AnabellaGamarnik, Andrea V.García, Cybele C.Iglesias, Néstor G.Vaz-Drago, RitaGarcía Solá, Martín E.Gebhard, Leopoldo G.Gaioli, NicolásTorti, María FlorenciaMammi, PabloBragado, LaureanoPozzi, Berta2022-06-06T13:48:25Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53279engNucleic Acids Res. 2020 Jul 9;48(12):6824-68380305-104810.1093/nar/gkaa3401362-4962info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:58:59Zoai:repositorio.ul.pt:10451/53279Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:15.518743Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response |
| title |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response |
| spellingShingle |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response Srebrow, Anabella |
| title_short |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response |
| title_full |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response |
| title_fullStr |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response |
| title_full_unstemmed |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response |
| title_sort |
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response |
| author |
Srebrow, Anabella |
| author_facet |
Srebrow, Anabella Gamarnik, Andrea V. García, Cybele C. Iglesias, Néstor G. Vaz-Drago, Rita García Solá, Martín E. Gebhard, Leopoldo G. Gaioli, Nicolás Torti, María Florencia Mammi, Pablo Bragado, Laureano Pozzi, Berta |
| author_role |
author |
| author2 |
Gamarnik, Andrea V. García, Cybele C. Iglesias, Néstor G. Vaz-Drago, Rita García Solá, Martín E. Gebhard, Leopoldo G. Gaioli, Nicolás Torti, María Florencia Mammi, Pablo Bragado, Laureano Pozzi, Berta |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Srebrow, Anabella Gamarnik, Andrea V. García, Cybele C. Iglesias, Néstor G. Vaz-Drago, Rita García Solá, Martín E. Gebhard, Leopoldo G. Gaioli, Nicolás Torti, María Florencia Mammi, Pablo Bragado, Laureano Pozzi, Berta |
| description |
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2022-06-06T13:48:25Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/53279 |
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http://hdl.handle.net/10451/53279 |
| dc.language.iso.fl_str_mv |
eng |
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eng |
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Nucleic Acids Res. 2020 Jul 9;48(12):6824-6838 0305-1048 10.1093/nar/gkaa340 1362-4962 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Oxford University Press |
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Oxford University Press |
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