Polypyrimidine Tract Binding Protein Regulates IRES-Mediated Gene Expression during Apoptosis

• Published in: Molecular cell Vol. 23; no. 3; pp. 401 - 412
• Main Authors: Bushell, Martin, Stoneley, Mark, Kong, Yi Wen, Hamilton, Tiffany L., Spriggs, Keith A., Dobbyn, Helen C., Qin, Xiaoli, Sarnow, Peter, Willis, Anne E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.08.2006
• Subjects: 5' Untranslated Regions - genetics; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Apoptosis - genetics; Apoptosis - physiology; Apoptosis Regulatory Proteins - pharmacology; Cell Cycle Proteins; Cell Line, Tumor; CELLCYCLE; DNA; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Humans; Membrane Glycoproteins - pharmacology; Oligonucleotide Array Sequence Analysis; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphorylation - drug effects; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Polypyrimidine Tract-Binding Protein - physiology; Polyribosomes - drug effects; Polyribosomes - metabolism; Protein Biosynthesis - drug effects; Protein Biosynthesis - genetics; Regulatory Sequences, Ribonucleic Acid - genetics; Ribosomes - metabolism; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; TNF-Related Apoptosis-Inducing Ligand; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Tumor Necrosis Factor-alpha - pharmacology; RNA; CELLCYCLE; DNA
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2006.06.012

During apoptosis there is a substantial reduction in the rate of protein synthesis, and yet some mRNAs avoid this translational inhibition. To determine the impact that receptor-mediated cell death has on the translational efficiency of a large number of mRNAs, translational profiling was performed on MCF7 cells treated with the apoptosis-inducing ligand TRAIL. Our data indicate that approximately 3% of mRNAs remain associated with the polysomes in apoptotic cells, and genes that are involved in transcription, chromatin modification/remodeling, and the Notch signaling pathway are particularly prevalent among the mRNAs that evade translational inhibition. Internal ribosome entry segments (IRESs) were identified in several of the mRNAs that remained associated with the polysomes during apoptosis, and, importantly, these IRESs functioned efficiently in apoptotic cells. Finally, the data showed that polypyrimidine tract binding protein (PTB, a known IRES trans-acting factor or ITAF) is pivotal in regulating the apoptotic process by controlling IRES function.