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Evolutionally conserved Nanos RNA-binding proteins play crucial roles in germ cell development. While a mammalian Nanos family protein, NANOS2, is required for sexual differentiation of male (XY) germ cells in mice, the underlying mechanisms and the identities of its target RNAs  in vivo  remain elusive. Using comprehensive microarray analysis and a bacterial artificial chromosome transgenic system, here we identify  Dazl , a germ cell-specific gene encoding an RNA-binding protein implicated in translation, as a crucial target of NANOS2. Importantly, removal of the  Dazl  3′-untranslated region in XY germ cells stabilizes the  Dazl  mRNA, resulting in elevated meiotic gene expression, abnormal resumption of the cell cycle and impaired processing-body formation, reminiscent of  Nanos2 -knockout phenotypes. Furthermore, our data suggest that NANOS2 acts as an antagonist of the DAZL protein. We propose a dual system of NANOS2-mediated suppression of  Dazl  expression as a pivotal molecular mechanism promoting sexual differentiation of XY germ cells.

Dazl is a target RNA suppressed by mammalian NANOS2 in sexually differentiating male germ cells