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Related Concept Videos

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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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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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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Nuclear Export01:42

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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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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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Directing Proteins to the Rough Endoplasmic Reticulum01:34

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The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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CRISPR-Mediated Reorganization of Chromatin Loop Structure
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A R-loop sensing pathway mediates the relocation of transcribed genes to nuclear pore complexes.

Arianna Penzo1, Marion Dubarry2,3, Clémentine Brocas4

  • 1Université Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, France.

Nature Communications
|September 20, 2023
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Nuclear pore complexes (NPCs) bind R-loops, genotoxic RNA-DNA hybrids. This relocation, triggered by R-loops themselves, involves RPA and SUMO, protecting genome stability.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Nuclear pore complexes (NPCs) interact with the genome, binding transcribed or damaged chromatin.
  • R-loops, formed by RNA-DNA hybridization, are genotoxic structures.
  • Understanding the link between NPCs, R-loops, and genome stability is crucial.

Purpose of the Study:

  • To investigate the correlation between NPC association and R-loop accumulation.
  • To determine the primary trigger for relocation to NPCs.
  • To elucidate the molecular mechanisms underlying R-loop-dependent NPC association and its functional significance.

Main Methods:

  • Genome-wide approaches combined with live imaging of model loci in yeast.
  • Manipulation of hybrid formation to assess R-loop accumulation.
  • Analysis of ssDNA-binding protein RPA and SUMO-dependent interactions.

Main Results:

  • A direct correlation was found between NPC association and R-loop accumulation.
  • R-loop accumulation per se, not transcription or damage, triggers relocation to NPCs.
  • R-loop-dependent repositioning involves RPA and SUMO-dependent NPC interactions.
  • Preventing relocation causes lethality under hybrid-accumulating conditions.
  • NPC tethering of hybrid-prone loci reduces genetic instability.

Conclusions:

  • R-loop accumulation is a primary trigger for relocation to NPCs.
  • This pathway, involving RPA and SUMO, is essential for genome stability under genotoxic stress.
  • Convergent mechanisms exist for sensing transcriptional and genotoxic stresses at NPCs.