Björkgren Ida, Sipilä Petra
Department of Physiology, Institute of Biomedicine; Laboratory Animal Centre, University of Helsinki, Helsinki, Finland.
Asian J Androl. 2015 Sep-Oct;17(5):737-41. doi: 10.4103/1008-682X.155542.
Dicer1 is an RNase III enzyme necessary for microRNA (miRNA) biogenesis, as it cleaves pre-miRNAs into mature miRNAs. miRNAs are important regulators of gene expression. In recent years, several miRNA-independent roles of Dicer1 have been identified. They include the production of endogenous small interfering RNAs, detoxifying retrotransposon-derived transcripts, and binding to new targets; messenger RNAs and long noncoding RNAs. Further, in this review, the functional significance of Dicer1 in the male reproductive tract is discussed. Conditional Dicer1 knock-out mouse models have demonstrated a requisite role for Dicer in male fertility. Deletion of Dicer1 from somatic or germ cells in the testis cause spermatogenic problems rendering male mice infertile. The lack of Dicer1 in the proximal epididymis causes dedifferentiation of the epithelium, with unbalanced sex steroid receptor expression, defects in epithelial lipid homeostasis, and subsequent male infertility. In addition, Dicer1 ablation from the prostate leads to increased apoptosis of the differentiated luminal cells, followed by epithelial hypotrophy of the ventral prostate. However, further studies are needed to clarify which functions of Dicer1 are responsible for the observed phenotypes in the male reproductive tract.
Dicer1是一种核糖核酸酶III,对微小RNA(miRNA)的生物合成至关重要,因为它能将前体miRNA切割成成熟的miRNA。miRNA是基因表达的重要调节因子。近年来,已发现Dicer1有几种不依赖miRNA的作用。它们包括产生内源性小干扰RNA、清除逆转录转座子衍生的转录本以及与新的靶标结合;信使RNA和长链非编码RNA。此外,在本综述中,还讨论了Dicer1在雄性生殖道中的功能意义。条件性Dicer1基因敲除小鼠模型已证明Dicer在雄性生育中起必要作用。从睾丸中的体细胞或生殖细胞中删除Dicer1会导致生精问题,使雄性小鼠不育。附睾近端缺乏Dicer1会导致上皮细胞去分化,性类固醇受体表达失衡,上皮脂质稳态缺陷,进而导致雄性不育。此外,从前列腺中切除Dicer1会导致分化的管腔细胞凋亡增加,随后腹侧前列腺上皮萎缩。然而,需要进一步研究来阐明Dicer1的哪些功能导致了在雄性生殖道中观察到的表型。