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
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DOI：
10.1261/rna.465507
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发表时间：
2007-07-01
期刊：
影响因子：
4.5
通讯作者：
Cooke, Howard J.
中科院分区：
文献类型：
--
作者：
Reynolds, Nicola;Collier, Brian;Cooke, Howard J.
DAZ相关基因对不同后生动物的配子发生是必不可少的：在人类男性中，DAZ基因的缺失与不育有关。这些基因只在生殖细胞中表达，调节着一组尚未确定的特定转录本的翻译，功能的丧失导致了生殖细胞发育的整个有丝分裂和减数分裂过程中的许多缺陷。在小鼠模型中，常染色体DAZL基因的缺失导致减数分裂前期合子线的最终阻断。Sycp3对减数分裂也是必不可少的，特别是对于联会复合体横向元件的形成，通过小鼠敲除模型显示在减数分裂前期显示一个类似于DAZL敲除的块。Sycp3被认为是DAZL在雄性小鼠生殖细胞中进行翻译调控的潜在靶点。RNA结合和翻译实验都证实了这一点。在DAZL基因敲除小鼠模型中，Sycp3蛋白水平降低，这表明DAZL是在体内有效翻译Sycp3mRNA所必需的。综上所述，这些数据支持Sycp3作为DAZL介导的哺乳动物翻译的生物学相关靶点。这表明人类中与DAZ基因功能降低相关的无精子症可能部分是由于SYCP3蛋白水平降低导致突触失败的结果。
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.