The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS.
Spi-1/PU.1 is an Ets protein deregulated by insertional mutagenesis during the murine Friend erythroleukemia. The overexpression of the normal protein in a proerythroblastic cell prevents its terminal differentiation. In normal hematopoiesis Spi-1/PU.1 is a transcription factor that plays a key role in normal myeloid and B lymphoid differentiation. Moreover, Spi-1/PU.1 ... binds RNA and interferes in vitro with the splicing process. Here we report that Spi-1 interacts in vivo with TLS (translocated in liposarcoma), a RNA-binding protein involved in human tumor-specific chromosomal translocations. This interaction appears functionally relevant, since TLS is capable of reducing the abilities of Spi-1/PU.1 to bind DNA and to transactivate the expression of a reporter gene. In addition, we observe that TLS is potentially a splicing factor. It promotes the use of the distal 5' splice site during the E1A pre-mRNA splicing. This effect is counterpoised in vivo by Spi-1. These data suggest that alteration of pre-mRNA alternative splicing by Spi-1 could be involved in the transformation of an erythroblastic cell.
Mesh Terms:
Alternative Splicing, Animals, Heterogeneous-Nuclear Ribonucleoproteins, Leukemia, Erythroblastic, Acute, Mice, Protein Binding, Proto-Oncogene Proteins, RNA-Binding Protein FUS, RNA-Binding Proteins, Ribonucleoproteins, Trans-Activators, Tumor Cells, Cultured
Alternative Splicing, Animals, Heterogeneous-Nuclear Ribonucleoproteins, Leukemia, Erythroblastic, Acute, Mice, Protein Binding, Proto-Oncogene Proteins, RNA-Binding Protein FUS, RNA-Binding Proteins, Ribonucleoproteins, Trans-Activators, Tumor Cells, Cultured
J. Biol. Chem.
Date: Feb. 27, 1998
PubMed ID: 9478924
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