MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
Shanghai Key Laboratory for Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, China.
Cell Death Dis. 2015 Jan 22;6(1):e1610. doi: 10.1038/cddis.2014.571.
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.
G-四链体 (G4) DNA 和 G4 DNA 解旋酶参与多种生物学过程。为了了解 G4 DNA 结构及其在精子发生中的解旋酶的生物学功能，我们研究了 G4 结构在小鼠睾丸中的分布，并鉴定了它们在精子发生过程中的变化。同时，我们使用具有精细胞特异性敲除小鼠模型研究了富含 AU 元件的 RNA 解旋酶相关蛋白 (RHAU)，一种 G4 DNA 解旋酶，在精子发生中的功能。结果表明，RHAU 在精细胞中的缺失导致 G4 结构的增加，从而导致精原细胞分化减少。c-kit 是一种与精原细胞分化相关的基因，其启动子上含有两个 G4 DNA 基序。我们发现其在 RHAU 条件性敲除睾丸中的表达显著下调。进一步的分析表明，RHAU 通过直接结合 G4 DNA 基序 c-kit 启动子来激活 c-kit 的表达。我们得出结论，RHAU 通过直接结合 c-kit 启动子上的 G4 DNA 基序来调节 c-kit 的表达，从而促进 c-kit 表达，从而调节精原细胞分化。
