Communication with the exon-junction complex and activation of nonsense-mediated decay by human Upf proteins occur in the cytoplasm.
Mol Cell
; 27(5): 780-92, 2007 Sep 07.
Article
en En
| MEDLINE
| ID: mdl-17803942
ABSTRACT
The nonsense-mediated mRNA decay (NMD) pathway rids eukaryotic cells of mRNAs with premature termination codons. There is contradictory evidence as to whether mammalian NMD is a nuclear or a cytoplasmic process. Here, we show evidence that NMD in human cells occurs primarily, if not entirely, in the cytoplasm. Polypeptides designed to inhibit interactions between NMD factors specifically impede NMD when exogenously expressed in the cytoplasm. However, restricting the polypeptides to the nucleus strongly impairs their NMD-inhibitory function, even for those intended to inhibit interactions between the exon-junction complex (EJC) and hUpf3 proteins, which localize primarily in the nucleus. NMD substrates classified based on cell fractionation assays as "nucleus associated" or "cytoplasmic" are all inhibited in the same manner. Furthermore, retention of the NMD factor hUpf1 in the nucleus strongly impairs NMD. These observations suggest that the hUpf complex communicates with the EJC and triggers NMD in the cytoplasm.
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Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Transactivadores
/
Proteínas de Unión al ARN
/
Codón sin Sentido
/
Estabilidad del ARN
/
Citoplasma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos