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. Weirich, Jan P. Erzberger, Jeffrey S. Flick, James M. Berger, Jeremy Thorner, Karsten Weis

Research output: Contribution to journalArticle

182 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)668-676
Number of pages9
JournalNature Cell Biology
Volume8
Issue number7
DOIs
StatePublished - Jul 1 2006

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Nuclear Pore
Porins
Nuclear Proteins
Messenger RNA
Proteins
Phytic Acid
Proton-Translocating ATPases
Cell Nucleus Active Transport
Adenosine Triphosphate
RNA
Phenotype
Mutation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. / Weirich, Christine S.; Erzberger, Jan P.; Flick, Jeffrey S.; Berger, James M.; Thorner, Jeremy; Weis, Karsten.

In: Nature Cell Biology, Vol. 8, No. 7, 01.07.2006, p. 668-676.

Research output: Contribution to journalArticle

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