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Directionality of Nuclear Transport01:42

Directionality of Nuclear Transport

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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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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.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
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Nuclear Protein Sorting01:34

Nuclear Protein Sorting

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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.
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...
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Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

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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...
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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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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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Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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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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Related Experiment Video

Updated: Sep 16, 2025

Method for the Isolation and Identification of mRNAs, microRNAs and Protein Components of Ribonucleoprotein Complexes from Cell Extracts using RIP-Chip
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Method for the Isolation and Identification of mRNAs, microRNAs and Protein Components of Ribonucleoprotein Complexes from Cell Extracts using RIP-Chip

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Structural basis for a nucleoporin exportin complex between RanBP2, SUMO1-RanGAP1, the E2 Ubc9, Crm1 and the Ran

Vladimir Baytshtok1, Michael A DiMattia1,2, Christopher D Lima3,4

  • 1Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, USA.

Nature Communications
|July 10, 2025
PubMed
Summary

The study reveals how RanBP2, a nuclear pore protein, interacts with SUMO1-modified RanGAP1 and Ubc9. These interactions are crucial for nuclear transport and mitotic progression, as shown by cryo-EM structures.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Structural Biology

Background:

  • RanBP2/Nup358 is a key nucleoporin involved in nuclear transport.
  • It interacts with SUMO1-modified RanGAP1 and Ubc9 at the nuclear pore complex (NPC).
  • This complex promotes the export and disassembly of exportin Crm1/Ran(GTP)/cargo complexes.

Purpose of the Study:

  • To resolve the cryo-EM structures of a RanBP2 C-terminal fragment in complex with Crm1, SUMO1-RanGAP1/Ubc9, and Ran(GTP).
  • To elucidate the structural basis for RanBP2's interactions with Crm1 and its role in nuclear transport and mitosis.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
  • Biochemical assays to validate structural findings.
  • Cellular localization studies to assess the function of key interactions.

Main Results:

  • Cryo-EM structures reveal detailed interactions between RanBP2, Crm1, SUMO1-RanGAP1/Ubc9, and Ran(GTP).
  • Identified a nuclear export signal (NES) for RanGAP1 within the Crm1 interaction interface.
  • Deletion of the RanGAP1 NES leads to mislocalization of RanGAP1 and Ran GTPase in cells.

Conclusions:

  • RanBP2's SUMO E3 ligase activity is dependent on Crm1, the RanGAP1 NES, and Ran GTPase cycling.
  • These findings support a model where RanBP2 facilitates nuclear export and mitotic progression through regulated interactions.