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Y 框结合蛋白 1 通过调控猪胚胎中 N6-甲基腺苷来影响合子基因组激活。

Y-box binding protein 1 influences zygotic genome activation by regulating N6-methyladenosine in porcine embryos.

机构信息

Department of Animal Science, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

出版信息

J Cell Physiol. 2023 Jul;238(7):1592-1604. doi: 10.1002/jcp.31040. Epub 2023 May 19.

Abstract

Y-box binding protein 1 (YBX1) is a member of the family of DNA- and RNA-binding proteins that play crucial roles in multiple aspects, including RNA stabilization, translational repression, and transcriptional regulation; however, its roles in embryo development remain less known. In this study, to investigate the function of YBX1 and its mechanism of action in porcine embryo development, YBX1 was knocked down by microinjecting YBX1 siRNA at the one-cell stage. YBX1 is located in the cytoplasm during embryonic development. The mRNA level of YBX1 was increased from the four-cell stage to the blastocyst stage but was significantly decreased in YBX1 knockdown embryos compared with the control. Moreover, the percentage of blastocysts was decreased following YBX1 knockdown compared with the control. Defecting YBX1 expression increased maternal gene mRNA expression and decreased zygotic genome activation (ZGA) gene mRNA expression and histone modification owing to decreased levels of N6-methyladenosine (m6A) writer N6-adenosine-methyltransferase 70 kDa subunit (METTL3) and reader insulin-like growth factor 2 mRNA-binding protein (IGF2BP1). In addition, IGF2BP1 knockdown showed that YBX1 regulated the ZGA process through m6A modification. In conclusion, YBX1 is essential for early embryo development because it regulates the ZGA process.

摘要

Y 盒结合蛋白 1(YBX1)是一种 DNA 和 RNA 结合蛋白家族的成员,在多个方面发挥着关键作用,包括 RNA 稳定、翻译抑制和转录调控;然而,其在胚胎发育中的作用知之甚少。在这项研究中,为了研究 YBX1 在猪胚胎发育中的功能及其作用机制,我们在一细胞期通过微注射 YBX1 siRNA 来敲低 YBX1。在胚胎发育过程中,YBX1 位于细胞质中。YBX1 的 mRNA 水平从四细胞期到囊胚期增加,但在 YBX1 敲低胚胎中与对照组相比显著降低。此外,与对照组相比,YBX1 敲低后囊胚的百分比下降。由于 N6-腺苷甲基转移酶 70kDa 亚基(METTL3)和胰岛素样生长因子 2mRNA 结合蛋白(IGF2BP1)等 m6A 写入器和读取器的水平降低,YBX1 表达缺陷会增加母体基因 mRNA 的表达,降低合子基因组激活(ZGA)基因 mRNA 的表达和组蛋白修饰。此外,IGF2BP1 敲低表明 YBX1 通过 m6A 修饰调节 ZGA 过程。总之,YBX1 对于早期胚胎发育是必不可少的,因为它调节 ZGA 过程。

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