Tags

Type your tag names separated by a space and hit enter

Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export.
Nat Cell Biol. 2006 Jul; 8(7):668-76.NC

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+Show Affiliations

Weirich CS
Division of Cell and Developmental Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
Erzberger JP
No affiliation info available
Flick JS
No affiliation info available
Berger JM
No affiliation info available
Thorner J
No affiliation info available
Weis K
No affiliation info available

MeSH

Active Transport, Cell NucleusBinding SitesCarrier ProteinsDEAD-box RNA HelicasesEnzyme ActivationMutationNuclear PoreNuclear Pore Complex ProteinsNucleocytoplasmic Transport ProteinsPhenotypePhytic AcidProtein Structure, TertiaryRNA HelicasesRNA, MessengerRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal Transduction

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16783364

Citation

Weirich, Christine S., et al. "Activation of the DExD/H-box Protein Dbp5 By the Nuclear-pore Protein Gle1 and Its Coactivator InsP6 Is Required for mRNA Export." Nature Cell Biology, vol. 8, no. 7, 2006, pp. 668-76.
Weirich CS, Erzberger JP, Flick JS, et al. Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nat Cell Biol. 2006;8(7):668-76.
Weirich, C. S., Erzberger, J. P., Flick, J. S., Berger, J. M., Thorner, J., & Weis, K. (2006). Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nature Cell Biology, 8(7), 668-76.
Weirich CS, et al. Activation of the DExD/H-box Protein Dbp5 By the Nuclear-pore Protein Gle1 and Its Coactivator InsP6 Is Required for mRNA Export. Nat Cell Biol. 2006;8(7):668-76. PubMed PMID: 16783364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. AU - Weirich,Christine S, AU - Erzberger,Jan P, AU - Flick,Jeffrey S, AU - Berger,James M, AU - Thorner,Jeremy, AU - Weis,Karsten, Y1 - 2006/06/18/ PY - 2006/03/31/received PY - 2006/05/19/accepted PY - 2006/6/20/pubmed PY - 2006/8/31/medline PY - 2006/6/20/entrez SP - 668 EP - 76 JF - Nature cell biology JO - Nat Cell Biol VL - 8 IS - 7 N2 - 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. SN - 1465-7392 UR - https://www.unboundmedicine.com/medline/citation/16783364/Activation_of_the_DExD/H_box_protein_Dbp5_by_the_nuclear_pore_protein_Gle1_and_its_coactivator_InsP6_is_required_for_mRNA_export_ DB - PRIME DP - Unbound Medicine ER -