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.