P bodies inhibit retrotransposition of endogenous intracisternal a particles

Chunye Lu1, Xavier Contreras, B Matija Peterlin

  • 1Department of Medicine, Microbiology, University of California at San Francisco, San Francisco, California 94143-0703, USA.

Journal of Virology
|April 29, 2011
PubMed

Insights

P bodies sequester messenger RNA (mRNA) away from Gag proteins, inhibiting the retrotransposition of intracisternal A-particle (IAP) elements in mammalian cells. Disrupting P bodies unexpectedly increased IAP retrotransposition and associated molecules.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • mRNA-processing bodies (P bodies) are cellular structures involved in mRNA regulation.
  • P bodies are known to play roles in the retrotransposition of certain elements in yeast.
  • The function of P bodies in mammalian retrotransposition, specifically for intracisternal A-particles (IAPs), was previously unclear.

Purpose of the Study:

  • To investigate the role of P bodies in the retrotransposition of endogenous intracisternal A particles (IAPs) in mammalian cells.
  • To determine whether P bodies promote or inhibit IAP retrotransposition.
  • To elucidate the mechanism by which P bodies might influence IAP replication.

Main Methods:

  • Knockdown of key P body components (RCK and eIF4E-T) to disrupt P bodies.
  • Quantification of IAP retrotransposition, IAP transcripts, Gag proteins, and reverse transcription products.
  • Analysis of IAP mRNA localization (P bodies vs. polysomes) and Gag protein targeting (endoplasmic reticulum).

Main Results:

  • Disruption of P bodies significantly increased IAP retrotransposition, IAP transcripts, Gag proteins, and reverse transcription products.
  • The observed increase was not due to microRNA pathway impairment.
  • P body disruption caused a shift of IAP mRNA from nonpolysomal to polysomal fractions.
  • IAP mRNA localized to P bodies, while Gag proteins were targeted to the endoplasmic reticulum for IAP budding.

Conclusions:

  • P bodies act as a mechanism to inhibit IAP retrotransposition in mammalian cells.
  • By sequestering IAP mRNA, P bodies prevent its translation and subsequent IAP assembly.
  • The findings reveal a novel regulatory role for P bodies in the life cycle of endogenous retroelements.

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