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11:48
Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in
Paul L Boutz1, Peter Stoilov, Qin Li
1Department of Microbiology, Immunology, and Molecular Genetics, 6-762 MacDonald Research Laboratories, Los Angeles, CA 90095, USA.
Genes & Development
|July 4, 2007
Summary
A switch between PTB and nPTB (neural PTB) proteins reprograms gene splicing during neuronal development. This switch, controlled post-transcriptionally, governs widespread alternative splicing essential for neuron maturation.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- Neuron-specific gene splicing is crucial for metazoan development but its control is unclear.
- Polypyrimidine tract-binding proteins (PTB) regulate alternative splicing.
- The paralog nPTB (neural PTB) is closely related to PTB, but its function is unknown.
Purpose of the Study:
- To investigate the developmental control of neuron-specific splicing.
- To determine the functional relationship between PTB and nPTB.
- To identify the role of PTB/nPTB switch in neuronal development.
Main Methods:
- Splicing-sensitive microarrays were used to identify exons regulated by PTB and nPTB.
- Expression patterns of PTB and nPTB proteins and mRNA were analyzed during neuronal development.
- Mechanisms of nPTB protein repression by PTB were investigated.
Main Results:
- A mutually exclusive expression pattern of PTB and nPTB proteins was observed in the brain.
- PTB represses nPTB protein expression in neuronal precursor cells (NPCs) and non-neuronal cells, partly via alternative splicing and nonsense-mediated decay (NMD).
- The switch from PTB to nPTB during neuronal differentiation correlates with altered splicing of specific exon sets.
Conclusions:
- A post-transcriptional switch from PTB to nPTB controls alternative splicing during neuronal development.
- This PTB/nPTB switch underlies a widespread alternative splicing program essential for neuronal maturation.
- PTB and nPTB act antagonistically to regulate gene expression during neurogenesis.
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