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MicroRNA dilution during oocyte growth disables the microRNA pathway in mammalian oocytes.
Nucleic Acids Research ( IF 14.9 ) Pub Date : 2020-07-01 , DOI: 10.1093/nar/gkaa543
Shubhangini Kataruka 1 , Martin Modrak 2 , Veronika Kinterova 3 , Radek Malik 1 , Daniela M Zeitler 4 , Filip Horvat 1, 5 , Jiri Kanka 3 , Gunter Meister 4 , Petr Svoboda 1
Affiliation  

MicroRNAs (miRNAs) are ubiquitous small RNAs guiding post-transcriptional gene repression in countless biological processes. However, the miRNA pathway in mouse oocytes appears inactive and dispensable for development. We propose that marginalization of the miRNA pathway activity stems from the constraints and adaptations of RNA metabolism elicited by the diluting effects of oocyte growth. We report that miRNAs do not accumulate like mRNAs during the oocyte growth because miRNA turnover has not adapted to it. The most abundant miRNAs total tens of thousands of molecules in growing (∅ 40 μm) and fully grown (∅ 80 μm) oocytes, a number similar to that observed in much smaller fibroblasts. The lack of miRNA accumulation results in a 100-fold lower miRNA concentration in fully grown oocytes than in somatic cells. This brings a knock-down-like effect, where diluted miRNAs engage targets but are not abundant enough for significant repression. Low-miRNA concentrations were observed in rat, hamster, porcine and bovine oocytes, arguing that miRNA inactivity is not mouse-specific but a common mammalian oocyte feature. Injection of 250,000 miRNA molecules was sufficient to restore reporter repression in mouse and porcine oocytes, suggesting that miRNA inactivity comes from low-miRNA abundance and not from some suppressor of the pathway.

中文翻译:

卵母细胞生长过程中的MicroRNA稀释会禁用哺乳动物卵母细胞中的microRNA途径。

微小RNA(miRNA)是无处不在的小RNA,在无数生物学过程中指导转录后基因的抑制。但是,小鼠卵母细胞中的miRNA途径似乎是无活性的,并且对于发育是必不可少的。我们提出,miRNA通路活性的边缘化是由于卵母细胞生长的稀释作用引起的RNA代谢的限制和适应。我们报道miRNA不会像卵母细胞生长过程中的mRNA一样积累,因为miRNA营业额不适应它。最丰富的miRNA在正在生长的卵母细胞(约40μm)和完全生长的卵母细胞(约80μm)中共有数万个分子,其数目与在更小的成纤维细胞中观察到的数目相似。缺乏miRNA积累会导致完全生长的卵母细胞中miRNA的浓度比体细胞中的miRNA浓度低100倍。这带来了类似的击倒效果,稀释的miRNA可以与靶标结合,但不足以显着抑制。在大鼠,仓鼠,猪和牛卵母细胞中观察到低的miRNA浓度,认为miRNA失活不是小鼠特异性的,而是哺乳动物卵母细胞的常见特征。注射250,000个miRNA分子足以恢复小鼠和猪卵母细胞中的报告基因阻遏,这表明miRNA的失活来自低miRNA的丰度,而不是某种途径的抑制物。
更新日期:2020-08-18
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