title: The DEAD-box protein Ded1 modulates translation by the formation and resolution of an eIF4F-mRNA complex.
abstract: The translation, localization, and degradation of cytoplasmic mRNAs are controlled by the formation and rearrangement of their mRNPs. The conserved Ded1/DDX3 DEAD-box protein functions in an unknown manner to affect both translation initiation and repression. We demonstrate that Ded1 first functions by directly interacting with eIF4G to assemble a Ded1-mRNA-eIF4F complex, which accumulates in stress granules. After ATP hydrolysis by Ded1, the mRNP exits stress granules and completes translation initiation. Thus, Ded1 functions both as a repressor of translation, by assembling an mRNP stalled in translation initiation, and as an ATP-dependent activator of translation, by resolving the stalled mRNP. These results identify Ded1 as a translation initiation factor that assembles and remodels an intermediate complex in translation initiation.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721-0206, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Hilliker
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Gao
authors.forename: Eckhard
authors.initials: E
authors.lastname: Jankowsky
authors.forename: Roy
authors.initials: R
authors.lastname: Parker
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D003594:Cytoplasmic Granules / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D005786:Gene Expression Regulation; D008957:Models, Genetic; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C026452:messenger ribonucleoprotein; D000255:Adenosine Triphosphate; C492152:DED1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases