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Translation inhibition during the induction of apoptosis: RNA or protein degradation?

M Bushell1, M Stoneley, P Sarnow

  • 1Department of Biochemistry, University of Leicester, University Rd, Leicester LE1 7RH, UK. martinbushelluk@yahoo.com

Biochemical Society Transactions
|July 24, 2004
PubMed

Insights

Apoptosis significantly inhibits protein synthesis by increasing mRNA degradation before key protein modifications. This accelerated mRNA decay is crucial for shutting down translation in cells undergoing programmed cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Apoptosis, or programmed cell death, involves significant cellular changes.
  • Protein synthesis is substantially inhibited during apoptosis.
  • Alterations in translation-initiation factors, ribosomes, and mRNA levels are known to occur.

Purpose of the Study:

  • To investigate the specific mechanisms responsible for translational shutdown during apoptosis.
  • To determine which modifications to the translational apparatus are essential for inhibiting protein synthesis.
  • To elucidate the role of mRNA degradation in this process.

Main Methods:

  • Analysis of modifications to the translational apparatus during apoptosis.
  • Examination of the temporal relationship between mRNA degradation and protein synthesis inhibition.
  • Assessment of caspase-dependent cleavage of initiation factors.

Main Results:

  • Global increase in mRNA degradation rate precedes caspase-dependent cleavage of initiation factors.
  • Increased mRNA decay is temporally correlated with translation shutdown.
  • This suggests mRNA decay plays a major role in inhibiting protein synthesis during apoptosis.

Conclusions:

  • Accelerated mRNA degradation is a key event in the inhibition of protein synthesis during apoptosis.
  • This process occurs before the modification of translation-initiation factors.
  • mRNA decay is a critical mechanism for achieving translational shutdown in apoptotic cells.

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