The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb.
The protooncogene for Spi-1/PU.1 is an Ets-related transcription factor overexpressed during Friend erythroleukemia. The molecular basis by which Spi-1/PU.1 is involved in the erythroleukemic process remains to be elucidated. By using an immobilized protein binding assay, we have identified a 55-kDa protein as a putative partner of Spi-1/PU.1 protein. Microsequence analysis revealed that this 55-kDa protein was p54nrb (nuclear RNA-binding protein, 54 kDa) a RNA-binding protein highly similar to the splicing factor PSF (polypyrimidine tract-binding protein-associated splicing factor). In this paper, we show that Spi-1/PU.1 impedes the binding of p54nrb to RNA and alters the splicing process in vitro. Moreover, we present evidence that the transcriptional factor Spi-1/PU.1, unlike other Ets proteins, is able to bind RNA. Altogether, these results raise the intriguing possibility that the functional interference observed between Spi-1/PU.1 and RNA-binding proteins might represent a novel mechanism in malignant erythropoiesis.
Hallier
M
M
INSERM, Unité 248, Institut Curie, Paris, France.
Tavitian
A
A
Moreau-Gachelin
F
F
D017398:Alternative Splicing; D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D004920:Erythropoiesis; D005622:Friend murine leukemia virus; D005914:Globins / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008970:Molecular Weight; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050810:Octamer Transcription Factors; D012313:RNA / Q000378:metabolism*; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; C062022:v-Spi-1 protein, Friend spleen focus-forming virus; D012313:RNA; D005914:Globins; D005982:Glutathione Transferase