While this report was in preparation, Maines and Was-serman reported that the Drosophila homologue of DAZL1—Boulc—controlledthetranslation ofTwine, a meiotic Cdc25-type phosphatase. They found that in boule mutants the translation, but not the transcription, of twine was significantly reduced, and that heterologous expression of Twine partially rescued the spermatogenic defect of bou-le mutants. Their results not only support our proposition that DAZL1 plays a role in translational regulation but also suggest Cdc25 transcripts as possible targets of DAZL1. Cdc25 phosphatases activate cyclin-dependent kinases and play an important role in cell cycle regulation. Three mammalian Cdc25 genes have been identified. Both Cdc25A and Cdc25C are expressed predominantly in the testis and could be the targets of DAZL1. However, DAZL1 is likely to have additional targets besides Cdc25, as suggested by the incomplete rescue of the boule phenotype by Twine. DAZL1 may facilitate the translation of its target genes by sequestering their transcripts to polysomes, by enhancing their translational rate, or by protecting the transcripts from degradation.
Whether DAZ is also involved in mRNA translation remains to be determined. It has been proposed that DAZ plays little, or a limited, role in spermatogenesis, on the basis of evolutionary considerations. The ability of a human DAZ transgene to rescue the spermatogenic defect of Dazl1 knock-out mice argues against such a proposal and suggests that DAZ serves a function similar to that of DAZL1. Structurally, DAZ and DAZL1 share high sequence identity except for the C-terminal segments. The RNA-binding characteristics of DAZ and DAZL1 are very similar. Whether DAZ is also associated with polysomes remains to be determined. Because DAZ is present in great apes and Old World monkeys only, its subcellular localization awaits the availability of testicular tissues from these higher mammals. If DAZ and DAZL1 are shown to serve a similar function, future studies could address the therapeutic potential of DAZL1 over-expression in infertile males with DAZ deletion.