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.
Reynolds
Nicola
N
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Collier
Brian
B
Bingham
Victoria
V
Gray
Nicola K
NK
Cooke
Howard J
HJ
D020413:3' Untranslated Regions / Q000032:analysis; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005260:Female; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000502:physiology*; D013573:Synaptonemal Complex / Q000737:chemistry / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C508515:DAZL protein, mouse; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C490062:Sycp3 protein, mouse