title: Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export.
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.
authors.affiliation: Division of Cell and Developmental Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Weirich
authors.forename: Jan P
authors.initials: JP
authors.lastname: Erzberger
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Flick
authors.forename: James M
authors.initials: JM
authors.lastname: Berger
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thorner
authors.forename: Karsten
authors.initials: K
authors.lastname: Weis
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053487:DEAD-box RNA Helicases; D004789:Enzyme Activation / Q000502:physiology; D009154:Mutation / Q000502:physiology; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010833:Phytic Acid / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C101408:GLE1 protein, S cerevisiae; C109212:NUP42 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D010833:Phytic Acid; C492382:DBP5 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases