The h subunit of eIF3 promotes reinitiation competence during translation of mRNAs harboring upstream open reading frames.
RNA
; 16(4): 748-61, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-20179149
ABSTRACT
Upstream open reading frames (uORFs) are protein coding elements in the 5' leader of messenger RNAs. uORFs generally inhibit translation of the main ORF because ribosomes that perform translation elongation suffer either permanent or conditional loss of reinitiation competence. After conditional loss, reinitiation competence may be regained by, at the minimum, reacquisition of a fresh methionyl-tRNA. The conserved h subunit of Arabidopsis eukaryotic initiation factor 3 (eIF3) mitigates the inhibitory effects of certain uORFs. Here, we define more precisely how this occurs, by combining gene expression data from mutated 5' leaders of Arabidopsis AtbZip11 (At4g34590) and yeast GCN4 with a computational model of translation initiation in wild-type and eif3h mutant plants. Of the four phylogenetically conserved uORFs in AtbZip11, three are inhibitory to translation, while one is anti-inhibitory. The mutation in eIF3h has no major effect on uORF start codon recognition. Instead, eIF3h supports efficient reinitiation after uORF translation. Modeling suggested that the permanent loss of reinitiation competence during uORF translation occurs at a faster rate in the mutant than in the wild type. Thus, eIF3h ensures that a fraction of uORF-translating ribosomes retain their competence to resume scanning. Experiments using the yeast GCN4 leader provided no evidence that eIF3h fosters tRNA reaquisition. Together, these results attribute a specific molecular function in translation initiation to an individual eIF3 subunit in a multicellular eukaryote.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Iniciação Traducional da Cadeia Peptídica
/
Fases de Leitura Aberta
/
Regiões 5' não Traduzidas
/
Subunidades Proteicas
/
Fator de Iniciação 3 em Eucariotos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
RNA
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos