Upf1 phosphorylation triggers translational repression during nonsense-mediated mRNA decay.
Cell
; 133(2): 314-27, 2008 Apr 18.
Article
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| MEDLINE
| ID: mdl-18423202
ABSTRACT
In mammalian cells, nonsense-mediated mRNA decay (NMD) generally requires that translation terminates sufficiently upstream of a post-splicing exon junction complex (EJC) during a pioneer round of translation. The subsequent binding of Upf1 to the EJC triggers Upf1 phosphorylation. We provide evidence that phospho-Upf1 functions after nonsense codon recognition during steps that involve the translation initiation factor eIF3 and mRNA decay factors. Phospho-Upf1 interacts directly with eIF3 and inhibits the eIF3-dependent conversion of 40S/Met-tRNA(i)(Met)/mRNA to translationally competent 80S/Met-tRNA(i)(Met)/mRNA initiation complexes to repress continued translation initiation. Consistent with phospho-Upf1 impairing eIF3 function, NMD fails to detectably target nonsense-containing transcripts that initiate translation independently of eIF3 from the CrPV IRES. There is growing evidence that translational repression is a key transition that precedes mRNA delivery to the degradation machinery. Our results uncover a critical step during NMD that converts a pioneer translation initiation complex to a translationally compromised mRNP.
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Bases de datos:
MEDLINE
Asunto principal:
Biosíntesis de Proteínas
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ARN Mensajero
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Transactivadores
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Estabilidad del ARN
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos