Artículo
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response
Pozzi, María Berta
; Bragado, Laureano Fabian Tomas
; Mammi, Pablo Andrés
; Torti, Maria Florencia; Gaioli, Nicolas Ezequiel
; Gebhard, Leopoldo German
; Garcia Sola, Martin Emilio
; Drago, Rita Vaz; Iglesias, Nestor Gabriel
; Garcia, Cybele
; Gamarnik, Andrea Vanesa
; Srebrow, Anabella
Fecha de publicación:
07/2020
Editorial:
Oxford University Press
Revista:
Nucleic Acids Research
ISSN:
0305-1048
e-ISSN:
1362-4962
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
RNA-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.
Palabras clave:
Dengue
,
RBM10
,
Polyamines
,
Splicing
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Colecciones
Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(OCA PQUE. CENTENARIO)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA PQUE. CENTENARIO
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA PQUE. CENTENARIO
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Pozzi, María Berta; Bragado, Laureano Fabian Tomas; Mammi, Pablo Andrés; Torti, Maria Florencia; Gaioli, Nicolas Ezequiel; et al.; Dengue virus targets RBM10 deregulating host cell splicing and innate immune response; Oxford University Press; Nucleic Acids Research; 48; 12; 7-2020; 6824-6838
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