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 developme ntal pathways, such as sex determination. There is emerging evidence sugges ting that RNA-binding proteins play a central role in regulation of develop ment in mammals as well. We are interested in spermatogenesis as a model fo r cell differentiation and development in mammals. Two Y-encoded candidate spermatogenesis genes, RBMY and DAZ, have been isolated by positional cloni ng from infertile patients. They both encode putative RNA-binding proteins of the RRM (RNA recognition motif) type, and the high degree of conservatio n of both these gene families suggests an important role in spermatogenesis . Mice with a null allele for Dazl1, the mouse homologue of DAZ, are infert ile due to a meiotic entry defect. Male flies mutant for boule, the Drosoph ila homologue of Dazl1, are infertile due to a G(2)/M meiotic block. Howeve r, no data has been published yet about the biochemical properties of the D AZ/DAZL1 proteins. We report here that Dazl1 is able to form homoheterodime rs 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. (C) 2000 Elsevier Science B.V. All rights reserved.