The transcription factor c-Myb affects pre-mRNA splicing.
c-Myb is a transcription factor which plays a key role in haematopoietic proliferation and lineage commitment. We raised the question of whether c-Myb may have abilities beyond the extensively studied transcriptional activation function. In this report we show that c-Myb influences alternative pre-mRNA splicing. This was seen by its marked effect on the 5'-splice site selection during E1A alternative splicing, while no effect of c-Myb was observed when reporters for the 3'-splice site selection or for the constitutive splicing process were tested. Moreover, co-immunoprecipitation experiments provided evidence for interactions between c-Myb and distinct components of the splicing apparatus, such as the general splicing factor U2AF(65) and hnRNPA1 involved in the 5'-splice site selection. The effect on 5'-splice site selection was abolished in the oncogenic variant v-Myb. Altogether, these data provide evidence that c-Myb may serve a previously unappreciated role in the coupling between transcription and splicing.
Orvain
Christophe
C
University of Oslo, Department of Molecular Biosciences, P.O. Box 1041 Blindern, N-0316 Oslo, Norway.
Matre
Vilborg
V
Gabrielsen
Odd S
OS
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism*; D022821:RNA Splice Sites; D012326:RNA Splicing; D012261:Ribonucleoproteins / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism; D000072668:Splicing Factor U2AF; D014158:Transcription, Genetic
D017500:Adenovirus E1A Proteins; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009687:Nuclear Proteins; D020598:Proto-Oncogene Proteins c-myb; D012322:RNA Precursors; D022821:RNA Splice Sites; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C000607494:U2AF2 protein, human; C000619656:hnRNPA1 protein, human