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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

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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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Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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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 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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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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Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
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Nuclear speckle integrity and function require TAO2 kinase.

Shengyan Gao1, Matthew Esparza1, Ishmael Dehghan2,3

  • 1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.

Proceedings of the National Academy of Sciences of the United States of America
|June 15, 2022
PubMed
Summary
This summary is machine-generated.

The protein kinase TAO2 is crucial for nuclear speckle structure and function, impacting messenger RNA (mRNA) splicing and influenza virus replication. Its depletion disrupts viral processes and host gene expression.

Keywords:
TAOK2mRNA exportnuclear specklessplicing

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Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • Nuclear speckles are key sites for mRNA processing and splicing.
  • These speckles are involved in the splicing and export of specific mRNAs, including influenza virus M mRNA.
  • The assembly and regulation of nuclear speckles remain poorly understood.

Purpose of the Study:

  • To investigate the role of the cellular protein kinase TAO2 in nuclear speckle formation and function.
  • To determine TAO2's impact on pre-mRNA splicing, nuclear export, and influenza virus replication.

Main Methods:

  • Localization studies to identify TAO2 within nuclear speckles.
  • Interaction assays with known nuclear speckle factors (SRSF1, Aly/Ref).
  • TAO2 depletion and kinase inhibition experiments.
  • Analysis of mRNA splicing, nuclear export, viral protein levels, and viral replication.

Main Results:

  • TAO2 is a constituent of nuclear speckles and is required for their integrity.
  • TAO2 interacts with splicing and nuclear export factors.
  • TAO2 depletion disrupts nuclear speckle structure and compromises influenza virus M mRNA splicing and export.
  • Reduced TAO2 levels inhibit viral replication and alter host mRNA expression.

Conclusions:

  • TAO2 plays a vital role in nuclear speckle assembly and function.
  • TAO2 is essential for efficient influenza virus replication.
  • TAO2 represents a potential host vulnerability for influenza infection.