The DEAD-Box Protein Ded1 Modulates Translation by the Formation and Resolution of an eIF4F-mRNA Complex

SummaryThe 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (76 K)Download as PowerPoint slideHighlights▸ Ded1 interacts directly with eIF4G to promote formation of a pre-translation complex ▸ Ded1 utilizes ATP to allow the mRNA-eIF4F-Ded1 complex to enter translation ▸ Ded1 can both repress and promote translation, depending on ATPase activity