Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 110(16): 6459-64, 2013 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-23553835

RESUMO

Retinoic acid inducible gene I (RIG-I) senses viral RNAs and triggers innate antiviral responses through induction of type I IFNs and inflammatory cytokines. However, whether RIG-I interacts with host cellular RNA remains undetermined. Here we report that Rig-I interacts with multiple cellular mRNAs, especially Nf-κb1. Rig-I is required for NF-κB activity via regulating Nf-κb1 expression at posttranscriptional levels. It interacts with the multiple binding sites within 3'-UTR of Nf-κb1 mRNA. Further analyses reveal that three distinct tandem motifs enriched in the 3'-UTR fragments can be recognized by Rig-I. The 3'-UTR binding with Rig-I plays a critical role in normal translation of Nf-κb1 by recruiting the ribosomal proteins [ribosomal protein L13 (Rpl13) and Rpl8] and rRNAs (18S and 28S). Down-regulation of Rig-I or Rpl13 significantly reduces Nf-κb1 and 3'-UTR-mediated luciferase expression levels. These findings indicate that Rig-I functions as a positive regulator for NF-κB signaling and is involved in multiple biological processes in addition to host antivirus immunity.


Assuntos
RNA Helicases DEAD-box/metabolismo , Regulação da Expressão Gênica/fisiologia , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Northern Blotting , Western Blotting , Proteína DEAD-box 58 , RNA Helicases DEAD-box/genética , Imunofluorescência , Imunoprecipitação , Luciferases , Camundongos , Camundongos Knockout , Análise em Microsséries , Simulação de Dinâmica Molecular , NF-kappa B/genética , Interferência de RNA , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Ribossômicas/metabolismo
2.
Cell Res ; 17(10): 858-68, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17893708

RESUMO

RIG-I (retinoid acid-inducible gene-I), a putative RNA helicase with a cytoplasmic caspase-recruitment domain (CARD), was identified as a pattern-recognition receptor (PRR) that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I(-/-) mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I(-/-) mice are viable and fertile. Histological analysis shows that Rig-I(-/-) mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer's patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation of T-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein alpha i2 subunit (G alpha i2) in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated G alpha i2 expression. Moreover, G alpha i2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of G alpha i2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of G alpha i2 and disturbed T-cell homeostasis.


Assuntos
Colite/genética , RNA Helicases DEAD-box/genética , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/genética , Animais , Apoptose/genética , Apoptose/fisiologia , Northern Blotting , Western Blotting , Células Cultivadas , Colite/induzido quimicamente , Colite/patologia , Proteína DEAD-box 58 , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/fisiologia , Sulfato de Dextrana/toxicidade , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/metabolismo , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/fisiologia , Camundongos , Camundongos Knockout , Células NIH 3T3 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/citologia , Linfócitos T/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...