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Originally published as MBC in Press, 10.1091/mbc.E07-12-1264 on July 2, 2008

Vol. 19, Issue 9, 3847-3858, September 2008

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The DEAD-Box RNA Helicase DDX3 Associates with Export Messenger Ribonucleoproteins as well asTip-associated Protein and Participates in Translational Control

Ming-Chih Lai*,{dagger}, Yan-Hwa Wu Lee{ddagger}, and Woan-Yuh Tarn*,{dagger}

*Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; {dagger}Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 144, Taiwan; and {ddagger}Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan

Submitted December 20, 2007; Revised June 19, 2008; Accepted June 25, 2008
Monitoring Editor: Peter Walter

Nuclear export of mRNA is tightly linked to transcription, nuclear mRNA processing, and subsequent maturation in the cytoplasm. Tip-associated protein (TAP) is the major nuclear mRNA export receptor, and it acts coordinately with various factors involved in mRNA expression. We screened for protein factors that associate with TAP and identified several candidates, including RNA helicase DDX3. We demonstrate that DDX3 directly interacts with TAP and that its association with TAP as well as mRNA ribonucleoprotein complexes may occur in the nucleus. Depletion of TAP resulted in nuclear accumulation of DDX3, suggesting that DDX3 is, at least in part, exported along with messenger ribonucleoproteins to the cytoplasm via the TAP-mediated pathway. Moreover, the observation that DDX3 localizes transiently in cytoplasmic stress granules under cell stress conditions suggests a role for DDX3 in translational control. Indeed, DDX3 associates with translation initiation complexes. However, DDX3 is probably not critical for general mRNA translation but may instead promote efficient translation of mRNAs containing a long or structured 5' untranslated region. Given that the DDX3 RNA helicase activity is essential for its involvement in translation, we suggest that DDX3 facilitates translation by resolving secondary structures of the 5'-untranslated region in mRNAs during ribosome scanning.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-12-1264) on July 2, 2008.

Address correspondence to: Woan-Yuh Tarn (wtarn{at}ibms.sinica.edu.tw)




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