title: Human DDX3 functions in translation and interacts with the translation initiation factor eIF3.
abstract: The conserved RNA helicase DDX3 is of major medical importance due to its involvement in numerous cancers, human hepatitis C virus (HCV) and HIV. Although DDX3 has been reported to have a wide variety of cellular functions, its precise role remains obscure. Here, we raised a new antibody to DDX3 and used it to show that DDX3 is evenly distributed throughout the cytoplasm at steady state. Consistent with this observation, HA-tagged DDX3 also localizes to the cytoplasm. RNAi of DDX3 in both human and Drosophila cells shows that DDX3 is required for cell viability. Moreover, using RNAi, we show that DDX3 is required for expression of protein from reporter constructs. In contrast, we did not detect a role for DDX3 in nuclear steps in gene expression. Further insight into the function of DDX3 came from the observation that its major interaction partner is the multi-component translation initiation factor eIF3. We conclude that a primary function for DDX3 is in protein translation, via an interaction with eIF3.
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Chung-Sheng
authors.initials: CS
authors.lastname: Lee
authors.forename: Anusha P
authors.initials: AP
authors.lastname: Dias
authors.forename: Mark
authors.initials: M
authors.lastname: Jedrychowski
authors.forename: Arvind H
authors.initials: AH
authors.lastname: Patel
authors.forename: Jeanne L
authors.initials: JL
authors.lastname: Hsu
authors.forename: Robin
authors.initials: R
authors.lastname: Reed
mesh_terms: D000818:Animals; D000906:Antibodies; D003593:Cytoplasm / Q000201:enzymology; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D034622:RNA Interference
chemical_list: D000906:Antibodies; D029721:Drosophila Proteins; D039621:Eukaryotic Initiation Factor-3; C531215:DDX3 protein, Drosophila; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases