Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl
Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl
DAZ-related genes are essential for gametogenesis in diverse metazoa: in human males, a loss of DAZ genes is associated with infertility. These genes, expressed only in germ cells, regulate the translation of a yet undefined set of specific transcripts, and loss of function results in numerous defects throughout the mitotic and meiotic process of germ cell development. In a mouse model, absence of the autosomal Dazl gene results in a final block at zygotene of meiotic prophase. Sycp3 is also essential for meiosis, specifically for the formation of the synaptonemal complex lateral element with a mouse knockout model displaying a block in meiotic prophase similar to the Dazl knock out. Sycp3 was identified as a potential target for translational regulation by Dazl in male mouse germ cells. This was confirmed by both RNA binding and translation assays. In the Dazl knockout mouse model, Sycp3 protein levels were decreased, indicating that Dazl is required for efficient translation of the Sycp3 mRNA in vivo. Taken together these data support Sycp3 as a biologically relevant target of Dazl-mediated translation in mammals. This suggests that azoospermia associated with a decrease in DAZ gene function in humans may in part be a consequence of failure at synapsis caused by reduced levels of SYCP3 protein.
- Imperial College Healthcare NHS Trust United Kingdom
- MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK United Kingdom
- Western General Hospital United Kingdom
- University of Edinburgh United Kingdom
- NHS Lothian United Kingdom
Male, Base Sequence, Synaptonemal Complex, Molecular Sequence Data, Nuclear Proteins, RNA-Binding Proteins, Cell Cycle Proteins, Mice, Transgenic, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Germ Cells, Gene Expression Regulation, Protein Biosynthesis, Testis, Animals, Humans, Female, 3' Untranslated Regions, Cells, Cultured
Male, Base Sequence, Synaptonemal Complex, Molecular Sequence Data, Nuclear Proteins, RNA-Binding Proteins, Cell Cycle Proteins, Mice, Transgenic, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Germ Cells, Gene Expression Regulation, Protein Biosynthesis, Testis, Animals, Humans, Female, 3' Untranslated Regions, Cells, Cultured
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