A direct role of SRY and SOX proteins in pre-mRNA splicing.
The mammalian testis determining factor SRY and its related Sox factors are critical developmental regulators. They share significant similarity in their high mobility group (HMG) domain and display discrete patterns of tissue-specific expression. Here we show that SRY and the Sox protein SOX6 colocalize with splicing factors in the nucleus and are dynamically redistributed following the blockage of splicing in living cells. Anti-SOX6 antibodies supershift the spliceosomal complex from assembled splicing reactions and inhibit splicing in vitro of multiple pre-mRNA substrates. Most importantly, SOX6-depleted nuclear extracts have impaired splicing activity, which is efficiently restored by addition of the recombinant SOX6 HMG domain and also by recombinant SRY and the SOX9 HMG domain. These results reveal an unexpected biological function of the SRY, SOX6, and SOX9 gene products and provide a functional link to the biochemical mechanisms operating in mammalian sex determination and in other developmental processes regulated by Sox genes.
Ohe
Kenji
K
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, B.P. 163, 67404 Illkirch-Strasbourg, France.
Lalli
Enzo
E
Sassone-Corsi
Paolo
P
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D003459:Crystallins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D051717:Fushi Tarazu Transcription Factors; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009687:Nuclear Proteins; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; D012733:Sex Differentiation; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors / Q000378:metabolism*; D014998:Y Chromosome
D003459:Crystallins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; C486270:SOX6 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055755:SOXD Transcription Factors; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; C497169:ftz protein, Drosophila