附睾特异性 RNase A 家族基因调控生育能力和小 RNA 处理。

IF 4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Joshua F Shaffer, Alka Gupta, Geetika Kharkwal, Edgardo E Linares, Andrew D Holmes, Julian R Swartz, Sol Katzman, Upasna Sharma
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引用次数: 0

摘要

精子小 RNA 与父代环境影响的代际传递有关。由 tRNA 分裂产生的小 RNA 被称为 tRNA 片段(tRFs)或 tRNA 衍生 RNA(tDRs 或 tsRNAs),是成熟精子中丰富的一类 RNA,可受环境条件的调节。人们对男性生殖道中 tRFs 的生物生成过程仍然知之甚少。Angiogenin是核糖核酸酶A超家族(RNase A)的成员,可在细胞应激时裂解tRNA,生成tRFs。Angiogenin的四个旁系亲属,即Rnase9、Rnase10、Rnase11和Rnase12,在附睾中特异性表达,附睾是精子成熟、获得生育能力和运动能力的长而曲折的小管。在这里,我们通过产生全部四个基因都被删除的小鼠(Rnase9-12-/-,称为 "KO",意为 "敲除"),报告了这些基因对生育力和小 RNA 水平的调控作用。KO雄性小鼠不育;KO精子能在体外使卵母细胞受精,但由于精子无法通过子宫-输卵管交界处,因此不能在体内有效地使卵母细胞受精。耐人寻味的是,KO 附睾和附睾管腔液中的 tRNAs(tRFs)和 rRNAs(rRNA 衍生的小 RNAs 或 rsRNAs)片段水平降低,尽管 RNase 9-12 在体外没有显示出核糖核酸溶解活性。重要的是,KO精子中的tRFs水平急剧下降,这表明附睾特异性Rnase9-12基因在调节精子小RNA组成方面发挥了作用。总之,我们的研究结果揭示了四个附睾特异性非经典 RNase A 家族基因在调节生育力和小 RNA 处理中的意外作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epididymis-specific RNase A family genes regulate fertility and small RNA processing.

Sperm small RNAs are implicated in intergenerational transmission of paternal environmental effects. Small RNAs generated by cleavage of tRNAs, known as tRNA fragments (tRFs) or tRNA-derived RNAs (tDRs or tsRNAs), are an abundant class of RNAs in mature sperm and can be modulated by environmental conditions. The biogenesis of tRFs in the male reproductive tract remains poorly understood. Angiogenin, a member of the Ribonuclease A superfamily (RNase A), cleaves tRNAs to generate tRFs in response to cellular stress. Four paralogs of Angiogenin, namely Rnase9, Rnase10, Rnase11, and Rnase12, are specifically expressed in the epididymis -a long, convoluted tubule where sperm mature and acquire fertility and motility. Here, by generating mice deleted for all four genes (Rnase9-12-/-, termed "KO" for Knock Out), we report that these genes regulate fertility and small RNA levels. KO male mice are sterile; KO sperm fertilized oocytes in vitro but failed to efficiently fertilize oocytes in vivo due to an inability of sperm to pass through the utero-tubular junction. Intriguingly, there were decreased levels of fragments of tRNAs (tRFs) and rRNAs (rRNA-derived small RNAs or rsRNAs) in the KO epididymis and epididymal luminal fluid, although RNases 9-12 did not show ribonucleolytic activity in-vitro. Importantly, KO sperm showed a dramatic decrease in the levels of tRFs, demonstrating a role of epididymis-specific Rnase9-12 genes in regulating sperm small RNA composition. Together, our results reveal an unexpected role of four epididymis-specific non-canonical RNase A family genes in regulating fertility and small RNA processing.

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来源期刊
Journal of Biological Chemistry
Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry
自引率
4.20%
发文量
1233
期刊介绍: The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.
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