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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
Published on: May 10, 2018
Polypyrimidine tract binding protein regulates IRES-mediated gene expression during apoptosis
Martin Bushell1, Mark Stoneley, Yi Wen Kong
1School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. martin.bushell@nottingham.ac.uk
Molecular Cell
|August 4, 2006
Summary
During apoptosis, some mRNAs evade protein synthesis inhibition. Internal ribosome entry segments (IRESs) enable efficient translation of these specific mRNAs, regulated by polypyrimidine tract binding protein (PTB).
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Apoptosis, or programmed cell death, involves a significant decrease in protein synthesis.
- However, certain messenger RNAs (mRNAs) escape this translational inhibition during apoptosis.
- Understanding which mRNAs are selectively translated is crucial for comprehending cell death pathways.
Purpose of the Study:
- To investigate the impact of receptor-mediated apoptosis on the translational efficiency of a broad range of mRNAs.
- To identify specific mRNA populations and regulatory mechanisms that facilitate translation during programmed cell death.
Main Methods:
- Translational profiling was conducted on MCF7 cells treated with Tumor necrosis factor receptor-associated death domain (TRAIL), an apoptosis-inducing ligand.
- Analysis focused on identifying mRNAs associated with polysomes in apoptotic cells.
Main Results:
- Approximately 3% of mRNAs remained associated with polysomes during apoptosis.
- Genes involved in transcription, chromatin modification/remodeling, and the Notch signaling pathway were enriched among these resilient mRNAs.
- Internal ribosome entry segments (IRESs) were identified in several of these mRNAs and demonstrated efficient function in apoptotic cells.
- Polypyrimidine tract binding protein (PTB), an IRES trans-acting factor (ITAF), was found to be critical for regulating IRES function during apoptosis.
Conclusions:
- Receptor-mediated apoptosis selectively preserves the translation of specific mRNAs, particularly those involved in key cellular processes.
- Internal ribosome entry segments (IRESs) play a significant role in enabling mRNA translation during apoptosis.
- The IRES trans-acting factor PTB is pivotal in controlling IRES-mediated translation during the apoptotic process.
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