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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS
M Hallier1, A Lerga, S Barnache
1INSERM U 248, Institut Curie, 26, rue d'Ulm, 75248 Paris Cedex 05, France.
The Journal of Biological Chemistry
|March 28, 1998
Summary
Spi-1/PU.1, a key transcription factor in blood cell development, interacts with TLS, a tumor-associated protein. This interaction impacts Spi-1/PU.1
Area of Science:
- Molecular Biology
- Hematopoiesis
- Oncology
Background:
- Spi-1/PU.1 is an Ets transcription factor crucial for myeloid and B lymphoid differentiation.
- Dysregulation of Spi-1/PU.1 is implicated in Friend erythroleukemia and blocks terminal differentiation.
- Spi-1/PU.1 exhibits RNA-binding capabilities and influences splicing processes.
Purpose of the Study:
- To investigate the in vivo interaction between Spi-1/PU.1 and the RNA-binding protein TLS.
- To elucidate the functional consequences of the Spi-1/PU.1 and TLS interaction on gene regulation and splicing.
- To explore the potential role of altered pre-mRNA splicing in erythroleukemia transformation.
Main Methods:
- In vivo interaction studies between Spi-1/PU.1 and TLS.
- Assessment of Spi-1/PU.1 DNA-binding and transactivation activities in the presence of TLS.
- Analysis of TLS-mediated effects on E1A pre-mRNA splicing and Spi-1/PU.1's counteraction.
Main Results:
- Spi-1/PU.1 directly interacts with TLS in vivo.
- TLS binding reduces Spi-1/PU.1's DNA-binding and transactivation capabilities.
- TLS promotes distal 5' splice site usage in E1A pre-mRNA splicing, an effect counteracted by Spi-1.
Conclusions:
- The interaction between Spi-1/PU.1 and TLS modulates their respective functions in DNA binding and splicing.
- Spi-1/PU.1's influence on alternative pre-mRNA splicing may contribute to erythroblastic cell transformation.
- TLS acts as a splicing factor, influencing alternative splicing events in a manner opposed by Spi-1.
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