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 du ring the murine Friend erythroleukemia. The overexpression of the norm al protein in a proerythroblastic cell prevents its terminal different iation. In normal hematopoiesis Spi-1/PU.1 is a transcription factor t hat plays a key role in normal myeloid and B lymphoid differentiation. Moreover, Spi-1/PU.1 binds RNA and interferes in vitro with the splic ing process. Here we report that Spi-1 interacts in vivo with TLS (tra nslocated in liposarcoma), a RNA-binding protein involved in human tum or-specific chromosomal translocations. This interaction appears funct ionally relevant, since TLS is capable of reducing the abilities of Sp i-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 fact or. It promotes the use of the distal 5' splice site during the E1A pr e-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.