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Related Concept Videos

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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Regulation of Nuclear Protein Sorting01:45

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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 Localization Signals and Import01:46

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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 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 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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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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Nuclear cGAS: guard or prisoner?

Carina C de Oliveira Mann1,2, Karl-Peter Hopfner1,2

  • 1Gene Center, Ludwig-Maximilians-Universität, Munich, Germany.

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|July 12, 2021
PubMed
Summary

The cyclic GMP-AMP synthase (cGAMP synthase) protein is found in the nucleus, interacting with chromatin to prevent self-DNA activation. This interaction regulates cGAS activity and cellular stress responses.

Keywords:
DNA sensingchromatincyclic GMP-AMP synthaseinnate immunitynucleosome

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The cyclic GMP-AMP synthase (cGAS) is a key sensor of innate immunity, detecting cytosolic DNA during infection or cellular stress.
  • Previously, cGAS was thought to be primarily cytosolic, but recent evidence indicates it is predominantly nuclear and chromatin-bound.
  • This nuclear localization raises questions about how cGAS remains inactive near self-DNA and its functional significance.

Purpose of the Study:

  • To explore the biological implications of nuclear cGAS localization.
  • To understand how nuclear cGAS interacts with chromatin and remains inactive.
  • To discuss mechanisms regulating cGAS activity within the nucleus.

Main Methods:

  • Cryo-electron microscopy (Cryo-EM) to determine structural interactions.
  • Analysis of protein-protein interactions between cGAS and nucleosomes.
  • Discussion of existing literature on cGAS regulation and function.

Main Results:

  • Cryo-EM structures show cGAS binding to nucleosomes, primarily via histones H2A/H2B.
  • These interactions physically block cGAS from binding DNA, preventing autoimmune responses.
  • Chromatin binding serves as a crucial inhibitory mechanism for nuclear cGAS.

Conclusions:

  • Nuclear localization of cGAS is critical for preventing autoreactivity to self-DNA.
  • Interactions with chromatin, particularly histones H2A/H2B, maintain cGAS in an inactive state.
  • Understanding nuclear cGAS regulation is vital for insights into innate immunity and autoimmunity.