DICER1 regulates antibacterial function of epididymis by modulating transcription of β-defensins.
DICER1 regulates antibacterial function of epididymis by modulating transcription of β-defensins.
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DICER1 通过调节 β-防御素的转录来调节附睾的抗菌功能
DOI：
10.1093/jmcb/mjy048
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发表时间：
2019-05-01
影响因子：
5.5
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Tang C;Ni M;Xie S;Zhang Y;Zhang C;Ni Z;Chu C;Wu L;Zhou Y;Zhang Y
摘要DICER 1是microRNA成熟的关键酶。最近的研究表明，DICER 1和microRNA在附睾中的表达与男性生育力的调控有关。然而，确切的机制仍有待阐明。在这里，我们建立了一个小鼠系的Dicer 1基因在附睾远端头的主细胞的靶向中断。我们的数据表明，一组β-防御素基因被DICER 1下调，而不是被microRNA下调。DICER 1基因在β-防御素基因启动子区富集，并控制转录。此外，Dicer 1基因缺失后，成年大鼠附睾的体外和体内抗菌能力均显著下降。在中年Dicer 1 −/−男性中观察到更高的生殖缺陷发生率。这些结果表明DICER 1在β-防御素基因的转录中起重要作用，β-防御素基因以不依赖于microRNA的方式与天然抗菌特性相关，并进一步影响男性生育力。
Abstract DICER1 is a key enzyme responsible for the maturation of microRNAs. Recent evidences suggested that DICER1 and microRNAs expressed in epididymis were involved in the control of male fertility. However, the exact mechanism remains to be elucidated. Here, we created a mouse line by targeted disruption of Dicer1 gene in the principal cells of distal caput epididymis. Our data indicated that a set of β-defensin genes were downregulated by DICER1 rather than by microRNAs. Moreover, DICER1 was significantly enriched in the promoter of β-defensin gene and controlled transcription. Besides, the antibacterial ability of the adult epididymis significantly declined upon Dicer1 deletion both in vitro and in vivo. And a higher incidence of reproductive defect was observed in middle-aged Dicer1−/− males. These results suggest that DICER1 plays an important role in transcription of β-defensin genes, which are associated with the natural antibacterial properties in a microRNA-independent manner, and further impacts the male fertility.
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