Characterization of signal sequences determining the nuclear export of Newcastle disease virus matrix protein

Zhiqiang Duan1, Qingqing Song, Yuyang Wang

  • 1Ministry of Education Key Lab for Avian Preventive Medicine, Yangzhou University, Yangzhou, Jiangsu, China.

Archives of Virology
|June 29, 2013
PubMed

Insights

The Newcastle disease virus (NDV) matrix (M) protein exports from the nucleus via three novel nuclear export signals (NESs). These NESs are independent of CRM1, a key protein in nuclear export, and are crucial for M protein function.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Newcastle disease virus (NDV) matrix (M) protein is essential for viral replication.
  • Previous research identified a nuclear localization signal (NLS) responsible for M protein entry into the nucleus.
  • The mechanism of M protein's nuclear export remained largely uncharacterized.

Purpose of the Study:

  • To elucidate the mechanism of nuclear export for the NDV M protein.
  • To identify the specific sequences mediating cytoplasmic localization of the M protein.
  • To determine the involvement of CRM1 in the M protein's nuclear export pathway.

Main Methods:

  • Site-directed mutagenesis to inactivate putative nuclear export signals (NESs) within the NDV M protein.
  • Leptomycin B (LMB) treatment to inhibit CRM1-dependent nuclear export.
  • Subcellular localization studies using microscopy to observe M protein distribution.

Main Results:

  • Three distinct NESs were identified as critical for the nuclear export of the NDV M protein.
  • Nuclear export mediated by these NESs was found to be CRM1-independent and LMB-insensitive.
  • Inactivation of the identified NESs resulted in the significant accumulation of the M protein within the nucleus.

Conclusions:

  • The identified NESs play a pivotal role in the CRM1-independent nuclear export of the NDV M protein.
  • These findings provide new insights into the nucleocytoplasmic trafficking of viral proteins.
  • Understanding these export mechanisms could inform antiviral strategies against NDV.

Related Concept Videos

Nuclear Export01:42

Nuclear Export

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...
Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

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...
Signal Sequences and Sorting Receptors01:41

Signal Sequences and Sorting Receptors

Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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...
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

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...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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...