Yang Guanghui, Xin Qiliang, Dean Jurrien
Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD, 20892, USA.
Adv Sci (Weinh). 2025 Jun;12(21):e2413599. doi: 10.1002/advs.202413599. Epub 2025 Apr 3.
Upon fertilization, the mouse zygotic genome is activated and maternal RNAs as well as proteins are degraded. Early developmental programs are built on proteins encoded by zygotic mouse genes that are needed to guide early cell fate commitment. The box C/D snoRNA ribonucleoprotein (snoRNP) complex is required for rRNA biogenesis, ribosome assembly and pre-mRNA splicing essential for protein translation. Zinc finger, HIT type 3 (encoded by Znhit3) is previously identified as a component in the assembly of the box C/D snoRNP complex. Using gene-edited mice, it identifies Znhit3 as an early embryonic gene whose ablation reduces protein translation and prevents mouse embryos development beyond the morula stage. The absence of ZNHIT3 leads to decreased snoRNA and rRNA abundance which causes defects of ribosomes and mRNA splicing. Microinjection of Znhit3 cRNA partially rescues the phenotype and confirms that ZNHIT3 is required for mRNA translation during preimplantation development.
受精后，小鼠合子基因组被激活，母源RNA和蛋白质被降解。早期发育程序建立在合子小鼠基因编码的蛋白质基础上，这些蛋白质是引导早期细胞命运决定所必需的。C/D盒小核仁RNA核糖核蛋白（snoRNP）复合物是rRNA生物合成、核糖体组装和蛋白质翻译所必需的前体mRNA剪接所必需的。锌指，HIT 3型（由Znhit3编码）先前被鉴定为C/D盒snoRNP复合物组装中的一个成分。利用基因编辑小鼠，它将Znhit3鉴定为一个早期胚胎基因，其缺失会减少蛋白质翻译并阻止小鼠胚胎发育超过桑椹胚阶段。ZNHIT3的缺失导致小核仁RNA和rRNA丰度降低，从而导致核糖体和mRNA剪接缺陷。显微注射Znhit3 cRNA可部分挽救该表型，并证实ZNHIT3在植入前发育期间对mRNA翻译是必需的。
