DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia
DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia
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DOI：
10.1038/s41467-019-09972-7
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发表时间：
2019-05-23
影响因子：
16.6
通讯作者：
Hobbs, Robin M.
中科院分区：
文献类型：
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作者：
Legrand, Julien M. D.;Chan, Ai-Leen;Hobbs, Robin M.
哺乳动物的精子发生是由有丝分裂的生殖细胞维持的，这种有丝分裂的生殖细胞具有自我更新的能力，称为未分化精原细胞。未分化精原细胞和精子发生的维持依赖于紧密协调的转录和转录后机制。精原细胞表达RNA解旋酶DDX5，但其在精子发生中的作用尚不清楚。使用可诱导的基因敲除小鼠模型，我们描述了DDX5在精原维持中的重要作用，并表明DDX5对于男性生育是不可或缺的。我们证明了DDX5调节精子发生所必需的关键基因的适当剪接。此外，DDX5在转录后调节未分化精原细胞中细胞周期基因的表达，是细胞增殖和生存所必需的。DDX5也可以作为转录共激活因子，我们证明了DDX5与PLZF相互作用，PLZF是维持生殖系所需的转录因子，共同调节选定的靶基因。综上所述，我们的数据揭示了DDX5在调节未分化精原细胞的基因表达程序和活性方面发挥着关键的多功能作用。
Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia.