期刊
EMBO JOURNAL
卷 31, 期 18, 页码 3745-3756出版社
WILEY
DOI: 10.1038/emboj.2012.220
关键词
DDX3; DEAD-box RNA helicase; eIF4F; HIV; translation initiation
资金
- Fondation pour la Recherche Medicale (FRM)
- ANRS
- 'Contrat d'Interface' with the Hospices Civils de Lyon
- CONICYT-Chile/ French Embassy doctoral fellowship
- Agence Nationale des Recherches sur le SIDA et les Hepatites Virales (ANRS) post-doctoral fellowship
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 50 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 50 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. The EMBO Journal (2012) 31, 3745-3756. doi: 10.1038/emboj.2012.220; Published online 7 August 2012
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