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Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export.
Nat Cell Biol. 2006 Jul; 8(7):711-6.NC

Abstract

Regulation of nuclear mRNA export is critical for proper eukaryotic gene expression. A key step in this process is the directional translocation of mRNA-ribonucleoprotein particles (mRNPs) through nuclear pore complexes (NPCs) that are embedded in the nuclear envelope. Our previous studies in Saccharomyces cerevisiae defined an in vivo role for inositol hexakisphosphate (InsP6) and NPC-associated Gle1 in mRNA export. Here, we show that Gle1 and InsP6 act together to stimulate the RNA-dependent ATPase activity of the essential DEAD-box protein Dbp5. Overexpression of DBP5 specifically suppressed mRNA export and growth defects of an ipk1 nup42 mutant defective in InsP6 production and Gle1 localization. In vitro kinetic analysis showed that InsP6 significantly increased Dbp5 ATPase activity in a Gle1-dependent manner and lowered the effective RNA concentration for half-maximal ATPase activity. Gle1 alone had minimal effects. Maximal InsP6 binding required both Dbp5 and Gle1. It has been suggested that Dbp5 requires unidentified cofactors. We now propose that Dbp5 activation at NPCs requires Gle1 and InsP6. This would facilitate spatial control of the remodelling of mRNP protein composition during directional transport and provide energy to power transport cycles.

Authors+Show Affiliations

Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U-3209 MRBIII, 465 21st Avenue South, Nashville, TN 37232-8240, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16783363

Citation

Alcázar-Román, Abel R., et al. "Inositol Hexakisphosphate and Gle1 Activate the DEAD-box Protein Dbp5 for Nuclear mRNA Export." Nature Cell Biology, vol. 8, no. 7, 2006, pp. 711-6.
Alcázar-Román AR, Tran EJ, Guo S, et al. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nat Cell Biol. 2006;8(7):711-6.
Alcázar-Román, A. R., Tran, E. J., Guo, S., & Wente, S. R. (2006). Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nature Cell Biology, 8(7), 711-6.
Alcázar-Román AR, et al. Inositol Hexakisphosphate and Gle1 Activate the DEAD-box Protein Dbp5 for Nuclear mRNA Export. Nat Cell Biol. 2006;8(7):711-6. PubMed PMID: 16783363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. AU - Alcázar-Román,Abel R, AU - Tran,Elizabeth J, AU - Guo,Shuangli, AU - Wente,Susan R, Y1 - 2006/06/18/ PY - 2006/03/13/received PY - 2006/04/21/accepted PY - 2006/6/20/pubmed PY - 2006/8/31/medline PY - 2006/6/20/entrez SP - 711 EP - 6 JF - Nature cell biology JO - Nat Cell Biol VL - 8 IS - 7 N2 - Regulation of nuclear mRNA export is critical for proper eukaryotic gene expression. A key step in this process is the directional translocation of mRNA-ribonucleoprotein particles (mRNPs) through nuclear pore complexes (NPCs) that are embedded in the nuclear envelope. Our previous studies in Saccharomyces cerevisiae defined an in vivo role for inositol hexakisphosphate (InsP6) and NPC-associated Gle1 in mRNA export. Here, we show that Gle1 and InsP6 act together to stimulate the RNA-dependent ATPase activity of the essential DEAD-box protein Dbp5. Overexpression of DBP5 specifically suppressed mRNA export and growth defects of an ipk1 nup42 mutant defective in InsP6 production and Gle1 localization. In vitro kinetic analysis showed that InsP6 significantly increased Dbp5 ATPase activity in a Gle1-dependent manner and lowered the effective RNA concentration for half-maximal ATPase activity. Gle1 alone had minimal effects. Maximal InsP6 binding required both Dbp5 and Gle1. It has been suggested that Dbp5 requires unidentified cofactors. We now propose that Dbp5 activation at NPCs requires Gle1 and InsP6. This would facilitate spatial control of the remodelling of mRNP protein composition during directional transport and provide energy to power transport cycles. SN - 1465-7392 UR - https://www.unboundmedicine.com/medline/citation/16783363/Inositol_hexakisphosphate_and_Gle1_activate_the_DEAD_box_protein_Dbp5_for_nuclear_mRNA_export_ DB - PRIME DP - Unbound Medicine ER -