Related Experiment Video

Updated: Aug 7, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export

Abel R Alcázar-Román1, Elizabeth J Tran, Shuangli Guo

  • 1Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U-3209 MRBIII, 465 21st Avenue South, Nashville, TN 37232-8240, USA.

Nature Cell Biology
|June 20, 2006
PubMed

Insights

Inositol hexakisphosphate (InsP6) and Gle1 protein work together to activate Dbp5, an essential protein for nuclear mRNA export in eukaryotic cells. This discovery clarifies the mechanism powering mRNA transport through nuclear pore complexes.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Nuclear mRNA export is vital for eukaryotic gene expression, involving the transport of mRNA-ribonucleoprotein particles (mRNPs) through nuclear pore complexes (NPCs).
  • Previous research identified inositol hexakisphosphate (InsP6) and NPC-associated Gle1 as crucial for mRNA export in Saccharomyces cerevisiae.

Purpose of the Study:

  • To investigate the functional relationship between Gle1, InsP6, and the DEAD-box protein Dbp5 in regulating nuclear mRNA export.
  • To elucidate the mechanism by which Gle1 and InsP6 modulate Dbp5 activity.

Main Methods:

  • Biochemical assays to measure RNA-dependent ATPase activity of Dbp5.
  • Genetic analysis involving overexpression of DBP5 in specific yeast mutants.
  • In vitro kinetic analysis of InsP6 binding and Dbp5 activity.

Main Results:

  • Gle1 and InsP6 synergistically stimulate the RNA-dependent ATPase activity of Dbp5.
  • Overexpression of DBP5 rescued mRNA export and growth defects in an ipk1 nup42 mutant.
  • InsP6 significantly enhanced Dbp5 ATPase activity in a Gle1-dependent manner, with maximal InsP6 binding requiring both Dbp5 and Gle1.

Conclusions:

  • Dbp5 activation at NPCs requires the combined action of Gle1 and InsP6.
  • This activation mechanism provides spatial control for mRNP remodeling during directional transport.
  • The findings suggest a model where Gle1 and InsP6 provide the energy necessary for mRNA transport cycles.

More Related Videos

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells10:12

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells

Published on: May 21, 2014

Xenopus laevis as a Model to Identify Translation Impairment10:24

Xenopus laevis as a Model to Identify Translation Impairment

Published on: September 27, 2015

Related Concept Videos

Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...