In vivo and in vitro analysis of homodimerisation activity of the mouse Dazl1 protein.
In Drosophila RNA-binding proteins play a fundamental role in key developmental pathways, such as sex determination. There is emerging evidence suggesting that RNA-binding proteins play a central role in regulation of development in mammals as well. We are interested in spermatogenesis as a model for cell differentiation and development in mammals. Two Y-encoded candidate spermatogenesis genes, RBMY and DAZ, have been isolated by positional cloning from infertile patients. They both encode putative RNA-binding proteins of the RRM (RNA recognition motif) type, and the high degree of conservation of both these gene families suggests an important role in spermatogenesis. Mice with a null allele for Dazl1, the mouse homologue of DAZ, are infertile due to a meiotic entry defect. Male flies mutant for boule, the Drosophila homologue of Dazl1, are infertile due to a G(2)/M meiotic block. However, no data has been published yet about the biochemical properties of the DAZ/DAZL1 proteins. We report here that Dazl1 is able to form homoheterodimers both in vivo and in vitro, that this activity is due to a novel protein-protein interaction domain, and that homotypic interaction activity is RNA-independent.
Ruggiu
M
M
MRC Human Genetics Unit, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, UK.
Cooke
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002846:Chromatography, Affinity; D004268:DNA-Binding Proteins; D000075364:Deleted in Azoospermia 1 Protein; D019281:Dimerization; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010957:Plasmids; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
C095668:DAZ1 protein, human; C101358:DAZL protein, human; D004268:DNA-Binding Proteins; D000075364:Deleted in Azoospermia 1 Protein; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011506:Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors