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Related Concept Videos

Nuclear Export01:42

Nuclear Export

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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.
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Nuclear Export of mRNA02:31

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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...
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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...
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Nuclear Protein Sorting01:34

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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.
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Directionality of Nuclear Transport01:42

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Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of  Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
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Regulated mRNA Transport02:22

Regulated mRNA Transport

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Related Experiment Video

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Analysis of mRNA Nuclear Export Kinetics in Mammalian Cells by Microinjection
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O-GlcNAc modulation of nuclear pore complexes orchestrates mRNA export efficiency.

Samuel L Junod1, Coby Rush1, Mark Tingey1

  • 1Department of Biology, Temple University, Philadelphia, PA 19122.

Proceedings of the National Academy of Sciences of the United States of America
|August 7, 2025
PubMed
Summary

O-linked N-acetylglucosamine (O-GlcNAc) modification of nuclear pore complexes (NPCs) regulates messenger RNA (mRNA) export. Altering O-GlcNAc levels impacts NPC structure and mRNA export efficiency, suggesting therapeutic potential for nuclear transport disorders.

Keywords:
O-GlcNAcmessenger RNAnuclear pore complexposttranslational modificationsuperresolution fluorescence microscopy

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Efficient gene expression relies on regulated mRNA export via nuclear pore complexes (NPCs).
  • NPCs are extensively modified by O-linked N-acetylglucosamine (O-GlcNAc), a dynamic post-translational modification.
  • Dysregulated O-GlcNAcylation is implicated in various human diseases, but its role in NPC function is unclear.

Purpose of the Study:

  • To investigate the precise distribution of O-GlcNAc within NPCs.
  • To quantify the impact of O-GlcNAcylation levels on mRNA export kinetics.
  • To explore the functional consequences of altered O-GlcNAc modification on NPC transport dynamics.

Main Methods:

  • Utilized single-point edge-excitation subdiffraction (SPEED) microscopy and stochastic optical reconstruction microscopy (STORM).
  • Mapped the nanometer-scale distribution of an O-GlcNAc analog (GlcNAz) within NPCs.
  • Quantified mRNA-protein complex (mRNP) export kinetics under varying O-GlcNAcylation conditions.

Main Results:

  • O-GlcNAc analog (GlcNAz) distribution shifts from the NPC central channel to peripheries under hypo- and hyper-O-GlcNAcylation.
  • Altered GlcNAz distribution correlates with changes in mRNP localization and nucleoporin arrangements.
  • Elevated O-GlcNAcylation increased mRNA export efficiency by ~61%, while reduced levels decreased it to ~16%.

Conclusions:

  • O-GlcNAcylation dynamically modulates NPC architecture and transport.
  • NPC O-GlcNAc levels are critical regulators of mRNA export efficiency.
  • Targeting NPC O-GlcNAc may offer therapeutic strategies for nuclear transport-related diseases.