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Stimuli-dependent cleavage of Dicer during apoptosis

Alexey A Matskevich1, Karin Moelling

  • 1Institute of Medical Virology, University of Zurich, Gloriastrasse 30/32, CH-8006 Zurich, Switzerland. matskevi@immv.unizh.ch

The Biochemical Journal
|February 22, 2008
PubMed

Insights

MicroRNA (miRNA) processing protein Dicer is cleaved during apoptosis, accelerating cell death. This cleavage is stimulus-dependent and observed in various apoptotic conditions, including HIV-1 infection.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • MicroRNAs (miRNAs) are crucial regulators of physiological processes like apoptosis and carcinogenesis.
  • While individual miRNA functions are known, proteins involved in miRNA production during stress are less studied.
  • Dicer is a key enzyme in miRNA biogenesis and processing.

Purpose of the Study:

  • To investigate the role of Dicer in apoptosis.
  • To determine if Dicer is a target of apoptotic pathways.
  • To examine Dicer cleavage in response to specific stimuli and conditions.

Main Methods:

  • Studied Dicer expression and function in HeLa cells undergoing apoptosis.
  • Investigated Dicer cleavage by caspases during apoptosis.
  • Examined Dicer integrity upon induction of apoptosis by tumor necrosis factor alpha (TNFα) and protein kinase C (PKC) inhibitors.
  • Analyzed Dicer cleavage in HIV-1-infected cells.

Main Results:

  • Down-regulation of Dicer accelerates TNFα-induced apoptosis in HeLa cells.
  • Dicer is cleaved by caspases during apoptosis, indicating it's a target.
  • Dicer cleavage is stimulus-dependent, being more pronounced with PKC inhibitors.
  • Dicer cleavage is observed in late-stage HIV-1 infection.

Conclusions:

  • The apoptotic machinery can regulate the miRNA pathway by targeting key proteins like Dicer.
  • Dicer cleavage by caspases is a mechanism linking apoptosis and miRNA regulation.
  • This finding has implications for understanding miRNA roles in viral infections and cancer.

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