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DEAD‐box protein DDX3 associates with eIF4F to promote translation of selected mRNAs
Author(s) -
SotoRifo Ricardo,
Rubilar Paulina S,
Limousin Taran,
de Breyne Sylvain,
Décimo Didier,
Ohlmann Théophile
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.220
Subject(s) - eif4g , biology , eif4e , internal ribosome entry site , eukaryotic initiation factor , initiation factor , eukaryotic translation , rna helicase a , eif4a , poly(a) binding protein , microbiology and biotechnology , translation (biology) , helicase , messenger rna , five prime untranslated region , rna , ribosomal binding site , stress granule , genetics , gene
Here, we have characterized a step in translation initiation of viral and cellular mRNAs that contain RNA secondary structures immediately at the vicinity of their m 7 GTP cap. This is mediated by the DEAD‐box helicase DDX3 which can directly bind to the 5′ of the target mRNA where it clamps the entry of eIF4F through an eIF4G and Poly A‐binding protein cytoplasmic 1 (PABP) double interaction. This could induce limited local strand separation of the secondary structure to allow 43S pre‐initiation complex attachment to the 5′ free extremity of the mRNA. We further demonstrate that the requirement for DDX3 is highly specific to some selected transcripts, cannot be replaced or substituted by eIF4A and is only needed in the very early steps of ribosome binding and prior to 43S ribosomal scanning. Altogether, these data define an unprecedented role for a DEAD‐box RNA helicase in translation initiation.