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Oncoprotein TLS interacts with serine-arginine proteins involved in RNA splicing
1Medical Research Service, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA.
The Journal of Biological Chemistry
|October 17, 1998
Summary
Researchers identified novel proteins interacting with the TLS (translocated lysosomal spectrin-like) protein, a key player in certain cancers. These interactions with splicing factors may explain how TLS gene fusions contribute to malignant transformation.
Area of Science:
- Molecular Biology
- Cancer Genetics
- RNA Splicing
Background:
- The TLS (FUS) gene is frequently involved in chromosomal translocations in human leukemias and sarcomas, forming fusion genes.
- These translocations often involve the C-terminal region of TLS, suggesting its functional importance.
Purpose of the Study:
- To identify proteins that interact with the TLS protein.
- To investigate the role of TLS-interacting proteins in RNA processing and malignant transformation.
Main Methods:
- Yeast two-hybrid screening of a mouse hematopoietic cDNA library using the C-terminal region of TLS.
- Co-transfection and immunoprecipitation assays to confirm protein interactions.
- In vivo splicing assays using adenovirus E1A pre-mRNA.
Main Results:
- Two serine-arginine (SR) proteins, splicing factor SC35 and a novel protein TASR (TLS-associated serine-arginine protein), were identified as TLS interactors.
- Mouse and human TASR proteins share identical amino acid sequences.
- SC35 and TASR were shown to influence splice site selection.
- TLS interacts with SR proteins via its C-terminal region.
Conclusions:
- TLS may recruit SR splicing factors to target genes through its C-terminal region.
- Truncation of the TLS C-terminus due to chromosomal translocations may disrupt this interaction.
- Altered RNA processing resulting from disrupted TLS-SR protein interaction could contribute to malignant transformation.