Article abstract
Nature Cell Biology 8, 668 - 676 (2006)
Published online: 18 June 2006 | doi:10.1038/ncb1424
Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export
Christine S. Weirich1, Jan P. Erzberger2, Jeffrey S. Flick3,4, James M. Berger2, Jeremy Thorner2 & Karsten Weis1
Abstract
The DExD/H-box ATPase Dbp5 is essential for nuclear mRNA export, although its precise role in this process remains poorly understood. Here, we identify the nuclear pore protein Gle1 as a cellular activator of Dbp5. Dbp5 alone is unable to stably bind RNA or effectively hydrolyse ATP under physiological conditions, but addition of Gle1 dramatically stimulates these activities. A gle1 point mutant deficient for Dbp5 stimulation in vitro displays an mRNA export defect in vivo, indicating that activation of Dbp5 is an essential function of Gle1. Interestingly, Gle1 binds directly to inositol hexakisphosphate (InsP6) and InsP6 potentiates the Gle1-mediated stimulation of Dbp5. Dominant mutations in DBP5 and GLE1 that rescue mRNA export phenotypes associated with the lack of InsP6 mimic the InsP6 effects in vitro. Our results define specific functions for Gle1 and InsP6 in mRNA export and suggest that local activation of Dbp5 at the nuclear pore is critical for mRNA export.
- Division of Cell and Developmental Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
- Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
- Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
- Current address: Myriad Pharmaceuticals Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA.
Correspondence to: Karsten Weis1 e-mail: kweis@berkeley.edu
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