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Published on: December 4, 2010

RNA nuclear export is blocked by poliovirus 2A protease and is concomitant with nucleoporin cleavage

Alfredo Castelló1, José M Izquierdo, Ewelina Welnowska

  • 1Centro de Biología Molecular, Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera, 1 Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.

Journal of Cell Science
|October 1, 2009
PubMed

Insights

Poliovirus 2A protease disrupts host cell RNA nuclear export by cleaving nucleoporins, specifically Nup98. Interferon-gamma partially prevents this inhibition, safeguarding new mRNA transport.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Cytopathic viruses employ mechanisms to evade host defenses and facilitate replication.
  • Understanding viral interference with host cell processes is crucial for antiviral development.

Purpose of the Study:

  • To investigate the impact of poliovirus 2A protease on RNA nuclear export.
  • To identify the specific viral and host factors involved in this process.

Main Methods:

  • Analysis of RNA trafficking in HeLa cells expressing poliovirus 2A protease.
  • Assessment of nucleoporin (Nup) cleavage and subcellular localization.
  • Evaluation of the effect of inactive protease and related viral proteases.
  • Investigation of interferon-gamma's role in modulating Nup98 levels and protease activity.

Main Results:

  • Poliovirus 2A protease inhibits the nuclear export of mRNAs, rRNAs, and U snRNAs, but not tRNAs.
  • Cleavage and redistribution of Nup98, Nup153, and Nup62 were observed in cells expressing active 2A protease.
  • Inactive 2A protease and other viral proteases (poliovirus 3C, FMDV L(pro)) did not affect RNA export or Nup98 integrity.
  • Interferon-gamma treatment increased Nup98 levels, leading to partial cleavage and prevention of RNA export inhibition.

Conclusions:

  • Poliovirus 2A protease specifically cleaves Nup98, thereby inhibiting the nuclear export of newly synthesized mRNAs.
  • This mechanism allows poliovirus to circumvent host antiviral responses and promote its replication.
  • Interferon-gamma exhibits a protective effect against poliovirus-induced RNA export blockage.

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