García-López Jesús, del Mazo Jesús
Department of Cell Proliferation and Development, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Biochim Biophys Acta. 2012 Aug;1819(8):847-54. doi: 10.1016/j.bbagrm.2012.03.007. Epub 2012 Mar 30.
The role of microRNAs (miRNAs) in early development, and particularly in the post-transcriptional regulation of maternal mRNAs remains controversial. Hence, we have assessed how miRNA processing is regulated during preimplantation mouse development, from the fully-grown oocyte to the blastocyst, quantifying the expression of genes whose proteins are involved in miRNAs biogenesis and function. The expression of the Drosha, Dgcr8, Exportin 5, Dicer, Ago1, Ago2, Ago3, Ago4 and Ago5 genes was downregulated from the zygotic cleavage stage, except for the increase of Ago1, Ago3 and Ago4 expression in the 2-cell embryo, and of Ago2 in 4- and 8-cell embryos. These findings suggest that the capacity to process miRNAs, by the considered canonical pathway, diminishes after fertilization, primarily reducing miRNA activity in the later stages of preimplantation development. However, by analyzing the different precursor and mature forms of specific miRNAs that are abundantly expressed in the blastocyst, such as miR-292-3p and miR-292-5p, we identified miRNA-duplexes and/or miRNAs bound to target mRNAs that may serve as potential stockpiles of miRNAs. In response to the demand, such stockpile could directly provide functional and mature miRNAs.
微小RNA(miRNA)在早期发育,尤其是在母源mRNA的转录后调控中的作用仍存在争议。因此,我们评估了从完全成熟的卵母细胞到囊胚的小鼠着床前发育过程中miRNA加工是如何被调控的,量化了其蛋白质参与miRNA生物合成和功能的基因的表达。Drosha、Dgcr8、Exportin 5、Dicer、Ago1、Ago2、Ago3、Ago4和Ago5基因的表达从合子分裂阶段开始下调,除了Ago1、Ago3和Ago4在2细胞胚胎中表达增加,以及Ago2在4细胞和8细胞胚胎中表达增加。这些发现表明,通过所考虑的经典途径加工miRNA的能力在受精后减弱,主要降低了着床前发育后期的miRNA活性。然而,通过分析囊胚中大量表达的特定miRNA的不同前体和成熟形式,如miR-292-3p和miR-292-5p,我们鉴定出了可能作为miRNA潜在储存库的miRNA双链体和/或与靶mRNA结合的miRNA。响应需求时,这种储存库可以直接提供功能性和成熟的miRNA。