A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation.
A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation.
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DOI：
10.1038/cddis.2014.571
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发表时间：
2015-01-22
影响因子：
9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Gao X;Ma W;Nie J;Zhang C;Zhang J;Yao G;Han J;Xu J;Hu B;Du Y;Shi Q;Yang Z;Huang X;Zhang Y
G-四链(G4)DNA和G4DNA解析酶参与多种生物学过程。为了了解G4DNA结构及其解旋酶在精子发生中的生物学功能，我们研究了G4结构在小鼠睾丸中的分布，并确定了它们在精子发生过程中的变化。同时，我们利用生殖细胞特异性基因敲除小鼠模型，研究了G4DNA解旋酶--富含AU元件的RNA解旋酶在精子发生中的作用。结果表明，切除生殖细胞中的RHAU导致G4结构增多，从而导致精原细胞分化减少。精原细胞分化相关基因C-KIT在其启动子上含有两个G4 DNA基序。我们发现其在RHAU条件性基因敲除睾丸中的表达显著下调。进一步分析表明，RHAU直接与G4结构结合，激活c-kit的表达。我们的结论是，RHAU通过直接与G4DNA基序c-kit启动子结合来促进c-kit的表达，从而调节精原细胞的分化。
G-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of biological processes. To understand the biological function of G4 DNA structures and their resolvases in spermatogenesis, we investigated the distribution of G4 structures in mouse testis and identified their alterations during spermatogenesis. Meanwhile, we studied the function of RNA helicase associated with AU-rich element (RHAU), a G4 DNA resolvase, in spermatogenesis with a germ-cell-specific knockout mouse model. The results showed that the ablation of RHAU in germ cells caused the increase of G4 structures and thus resulted in the decrease of spermatogonial differentiation. c-kit, a spermatogonia differentiation-related gene, contains two G4 DNA motifs on its promoter. We found its expression was significantly downregulated in RHAU conditional knockout testis. A further analysis demonstrated that RHAU directly bound to the G4 structures to activate c-kit expression. We concluded that RHAU regulates spermatogonia differentiation by promoting c-kit expression via directly binding to the G4 DNA motifs c-kit promoter.