Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, 410078, Changsha, China.
Life Sciences Institute, Zhejiang University, 310058, Hangzhou, China.
Nat Commun. 2022 Nov 4;13(1):6621. doi: 10.1038/s41467-022-34427-x.
Protein synthesis is an essential step in gene expression during the development of mammalian preimplantation embryos. This is a complex and highly regulated process. The accuracy of the translation initiation codon is important in various gene expression programs. However, the mechanisms that regulate AUG and non-AUG codon initiation in early embryos remain poorly understood. BZW1 is a key factor in determining the mRNA translation start codon. Here, we show that BZW1 is essential for early embryonic development in mice. Bzw1-knockdown embryos fail to undergo compaction, and show decreased blastocyst formation rates. We also observe defects in the differentiation capacity and implantation potential after Bzw1 interference. Further investigation revealed that Bzw1 knockdown causes the levels of translation initiation with CUG as the start codon to increase. The decline in BZW1 levels result in a decrease in protein synthesis in preimplantation embryos, whereas the total mRNA levels are not altered. Therefore, we concluded that BZW1 contributes to protein synthesis during early embryonic development by restricting non-AUG translational initiation.
蛋白质合成是哺乳动物胚胎植入前发育过程中基因表达的一个必要步骤。这是一个复杂且高度调控的过程。翻译起始密码子的准确性在各种基因表达程序中都很重要。然而，调节早期胚胎中 AUG 和非 AUG 密码子起始的机制仍知之甚少。BZW1 是决定 mRNA 翻译起始密码子的关键因素。在这里，我们表明 BZW1 对于小鼠早期胚胎发育是必需的。Bzw1 敲低胚胎无法进行致密化，囊胚形成率降低。我们还观察到 Bzw1 干扰后的分化能力和植入潜力缺陷。进一步的研究表明，Bzw1 敲低导致以 CUG 为起始密码子的翻译起始水平增加。BZW1 水平的下降导致植入前胚胎中蛋白质合成减少，而总 mRNA 水平没有改变。因此，我们得出结论，BZW1 通过限制非 AUG 翻译起始来促进早期胚胎发育过程中的蛋白质合成。
