Kim Kyeoung-Hwa, Seo You-Mi, Kim Eun-Young, Lee Su-Yeon, Kwon Jini, Ko Jung-Jae, Lee Kyung-Ah
Institute of Reproductive Medicine, Department of Biomedical Science, College of Life Science, CHA University, Pangyo, South Korea.
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, South Korea.
Open Biol. 2016 Nov;6(11). doi: 10.1098/rsob.160181.
Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify such regulatory microRNAs (miRNAs) and to determine the effects of the identified miRNAs on Sebox expression. Using computational algorithms, we identified a motif within the 3'UTR of Sebox mRNA that is specific to the seed region of the miR-125 family, which includes miR-125a-5p, miR-125b-5p and miR-351-5p. During our search for miRNAs, we found that the Lin28a 3'UTR also contains the same binding motif for the seed region of the miR-125 family. In addition, we confirmed that Lin28a also plays a role as a MEG and affects ZGA at the 2C stage, without affecting oocyte maturation or fertilization. Thus, we provide the first report indicating that the miR-125 family plays a crucial role in regulating MEGs related to the 2C block and in regulating ZGA through methods such as affecting Sebox and Lin28a in oocytes and embryos.
此前，我们报道过Sebox是一种新的母体效应基因（MEG），它是两细胞（2C）期之后早期胚胎发育所必需的，因为该基因协调合子基因组激活（ZGA）重要基因的表达。然而，Sebox表达的调节因子仍然未知。因此，本研究的目的是使用生物信息学工具来鉴定此类调节性微小RNA（miRNA），并确定所鉴定的miRNA对Sebox表达的影响。通过计算算法，我们在Sebox mRNA的3'非翻译区（UTR）内鉴定出一个特定于miR-125家族种子区域的基序，该家族包括miR-125a-5p、miR-125b-5p和miR-351-5p。在我们寻找miRNA的过程中，我们发现Lin28a的3'UTR也含有与miR-125家族种子区域相同的结合基序。此外，我们证实Lin28a也作为一种MEG发挥作用，并在2C期影响ZGA，而不影响卵母细胞成熟或受精。因此，我们首次报道表明miR-125家族在调节与2C阻滞相关的MEG以及通过影响卵母细胞和胚胎中的Sebox和Lin28a等方式调节ZGA方面发挥着关键作用。
