The SKIV2L RNA exosome limits activation of the RIG-I-like receptors.
Nat Immunol
; 15(9): 839-45, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-25064072
ABSTRACT
Sensors of the innate immune system that detect intracellular nucleic acids must be regulated to prevent inappropriate activation by endogenous DNA and RNA. The exonuclease Trex1 regulates the DNA-sensing pathway by metabolizing potential DNA ligands that trigger it. However, an analogous mechanism for regulating the RIG-I-like receptors (RLRs) that detect RNA remains unknown. We found here that the SKIV2L RNA exosome potently limited the activation of RLRs. The unfolded protein response (UPR), which generated endogenous RLR ligands through the cleavage of cellular RNA by the endonuclease IRE-1, triggered the production of type I interferons in cells depleted of SKIV2L. Humans with deficiency in SKIV2L had a type I interferon signature in their peripheral blood. Our findings reveal a mechanism for the intracellular metabolism of immunostimulatory RNA, with implications for specific autoimmune disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Proteínas de Ligação a RNA
/
Proteínas Serina-Treonina Quinases
/
RNA Helicases
/
Diarreia Infantil
/
Endorribonucleases
/
RNA Helicases DEAD-box
/
Resposta a Proteínas não Dobradas
/
Retardo do Crescimento Fetal
/
Complexo Multienzimático de Ribonucleases do Exossomo
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos