title: DEAD-box protein DDX3 associates with eIF4F to promote translation of selected mRNAs.
abstract: 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.
authors.affiliation: Human Virology Department, INSERM U, Lyon, France.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Soto-Rifo
authors.forename: Paulina S
authors.initials: PS
authors.lastname: Rubilar
authors.forename: Taran
authors.initials: T
authors.lastname: Limousin
authors.forename: Sylvain
authors.initials: S
authors.lastname: de Breyne
authors.forename: Didier
authors.initials: D
authors.lastname: Décimo
authors.forename: Théophile
authors.initials: T
authors.lastname: Ohlmann
mesh_terms: D020121:5' Untranslated Regions; D020816:Amino Acid Motifs; D001665:Binding Sites; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D005786:Gene Expression Regulation; D006678:HIV / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009690:Nucleic Acid Conformation; D039122:Poly(A)-Binding Protein I / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry
chemical_list: D020121:5' Untranslated Regions; D039562:Eukaryotic Initiation Factor-4F; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases