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The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1.
Genes Dev. 2011 May 15; 25(10):1065-77.GD

Abstract

Essential messenger RNA (mRNA) export factors execute critical steps to mediate directional transport through nuclear pore complexes (NPCs). At cytoplasmic NPC filaments, the ATPase activity of DEAD-box protein Dbp5 is activated by inositol hexakisphosphate (IP(6))-bound Gle1 to mediate remodeling of mRNA-protein (mRNP) complexes. Whether a single Dbp5 executes multiple remodeling events and how Dbp5 is recycled are unknown. Evidence suggests that Dbp5 binding to Nup159 is required for controlling interactions with Gle1 and the mRNP. Using in vitro reconstitution assays, we found here that Nup159 is specifically required for ADP release from Dbp5. Moreover, Gle1-IP(6) stimulates ATP binding, thus priming Dbp5 for RNA loading. In vivo, a dbp5-R256D/R259D mutant with reduced ADP binding bypasses the need for Nup159 interaction. However, NPC spatial control is important, as a dbp5-R256D/R259D nup42Δ double mutant is temperature-sensitive for mRNA export. Further analysis reveals that remodeling requires a conformational shift to the Dbp5-ADP form. ADP release factors for DEAD-box proteins have not been reported previously and reflect a new paradigm for regulation. We propose a model wherein Nup159 and Gle1-IP(6) regulate Dbp5 cycles by controlling its nucleotide-bound state, allowing multiple cycles of mRNP remodeling by a single Dbp5 at the NPC.

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Authors+Show Affiliations

Noble KN
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Tran EJ
No affiliation info available
Alcázar-Román AR
No affiliation info available
Hodge CA
No affiliation info available
Cole CN
No affiliation info available
Wente SR
No affiliation info available

MeSH

Active Transport, Cell NucleusAdenosine DiphosphateAdenosine TriphosphateCell NucleusDEAD-box RNA HelicasesMutationNuclear PoreNuclear Pore Complex ProteinsNucleocytoplasmic Transport ProteinsNucleotidesProtein BindingProtein ConformationRNA, MessengerRibonucleoproteinsSaccharomyces cerevisiae Proteins

Pub Type(s)

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

Language

eng

PubMed ID

21576266

Citation

Noble, Kristen N., et al. "The Dbp5 Cycle at the Nuclear Pore Complex During mRNA Export II: Nucleotide Cycling and mRNP Remodeling By Dbp5 Are Controlled By Nup159 and Gle1." Genes & Development, vol. 25, no. 10, 2011, pp. 1065-77.
Noble KN, Tran EJ, Alcázar-Román AR, et al. The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1. Genes Dev. 2011;25(10):1065-77.
Noble, K. N., Tran, E. J., Alcázar-Román, A. R., Hodge, C. A., Cole, C. N., & Wente, S. R. (2011). The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1. Genes & Development, 25(10), 1065-77. https://doi.org/10.1101/gad.2040611
Noble KN, et al. The Dbp5 Cycle at the Nuclear Pore Complex During mRNA Export II: Nucleotide Cycling and mRNP Remodeling By Dbp5 Are Controlled By Nup159 and Gle1. Genes Dev. 2011 May 15;25(10):1065-77. PubMed PMID: 21576266.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1. AU - Noble,Kristen N, AU - Tran,Elizabeth J, AU - Alcázar-Román,Abel R, AU - Hodge,Christine A, AU - Cole,Charles N, AU - Wente,Susan R, PY - 2011/5/18/entrez PY - 2011/5/18/pubmed PY - 2011/7/8/medline SP - 1065 EP - 77 JF - Genes & development JO - Genes Dev VL - 25 IS - 10 N2 - Essential messenger RNA (mRNA) export factors execute critical steps to mediate directional transport through nuclear pore complexes (NPCs). At cytoplasmic NPC filaments, the ATPase activity of DEAD-box protein Dbp5 is activated by inositol hexakisphosphate (IP(6))-bound Gle1 to mediate remodeling of mRNA-protein (mRNP) complexes. Whether a single Dbp5 executes multiple remodeling events and how Dbp5 is recycled are unknown. Evidence suggests that Dbp5 binding to Nup159 is required for controlling interactions with Gle1 and the mRNP. Using in vitro reconstitution assays, we found here that Nup159 is specifically required for ADP release from Dbp5. Moreover, Gle1-IP(6) stimulates ATP binding, thus priming Dbp5 for RNA loading. In vivo, a dbp5-R256D/R259D mutant with reduced ADP binding bypasses the need for Nup159 interaction. However, NPC spatial control is important, as a dbp5-R256D/R259D nup42Δ double mutant is temperature-sensitive for mRNA export. Further analysis reveals that remodeling requires a conformational shift to the Dbp5-ADP form. ADP release factors for DEAD-box proteins have not been reported previously and reflect a new paradigm for regulation. We propose a model wherein Nup159 and Gle1-IP(6) regulate Dbp5 cycles by controlling its nucleotide-bound state, allowing multiple cycles of mRNP remodeling by a single Dbp5 at the NPC. SN - 1549-5477 UR - https://www.unboundmedicine.com/medline/citation/21576266/The_Dbp5_cycle_at_the_nuclear_pore_complex_during_mRNA_export_II:_nucleotide_cycling_and_mRNP_remodeling_by_Dbp5_are_controlled_by_Nup159_and_Gle1_ DB - PRIME DP - Unbound Medicine ER -