Nucleic Acids Research Advance Access originally published online on July 15, 2008
Nucleic Acids Research 2008 36(14):4708-4718; doi:10.1093/nar/gkn454
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Nucleic Acids Research, 2008, Vol. 36, No. 14 4708-4718
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Human DDX3 functions in translation and interacts with the translation initiation factor eIF3
1Department of Cell Biology, 2Taplin Biological Mass Spectrometry Facility, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA and 3MRC Virology Unit, Church Street, Glasgow G11 5JR, UK
*To whom correspondence should be addressed. Tel: +(617) 432-2844; Fax: +(617) 432-3091; Email: rreed{at}hms.harvard.edu
Received May 15, 2008. Revised June 27, 2008. Accepted June 30, 2008.
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.
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