该研究组观察到在8细胞ZGA阶段阻滞的人类胚胎表现出内源性逆转录病毒MLT2A1的特异性下调。耗尽MLT2A1导致胚胎发育失败和ZGA基因表达减少。从机制上讲，MLT2A1s与下游编码和非编码序列合成嵌合转录本，主要是与异位逆转录因子。这些不同的离子序列扩展了MLT2A1 RNAs的基因组靶向谱。然而，共享的MLT2A1序列与异质核核糖核蛋白U （HNRNPU）合作募集RNA聚合酶II，促进ZGA基因的全球转录和MLT2A1亚家族的自身扩增。因此，MLT2A1嵌合RNAs形成了一个互锁网络，协同作用促进人类ZGA和早期胚胎发生。
研究人员表示，合子基因组激活（ZGA）失败导致发育停滞，并对妇女生育能力提出了临床挑战。
附：英文原文
Title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development
Author: Yangquan Xiang, Yuli Qian, Zhengyi Li, Jiaxu Wang, Ruonan Tian, Weikang Meng, Jiabao Bu, Fei Huang, Zhipeng Ai, Danya Wu, Xijia Chen, You Wu, Li Shen, Yun-Shen Chan, Yawei Gao, Jun Ma, Wanlu Liu, Shaorong Gao, Dan Zhang, Hongqing Liang
Issue&Volume: 2026-01-22
Abstract: Zygotic genome activation (ZGA) failure leads to developmental arrest and poses a clinical challenge to women’s fertility. We observed that human embryos arresting at the eight-cell ZGA stage exhibited specific down-regulation of endogenous retrovirus MLT2A1. Depleting MLT2A1 resulted in a failure in embryo development and a reduction in ZGA gene expression. Mechanistically, MLT2A1s synthesized chimeric transcripts with downstream coding and noncoding sequences, predominantly with heterologous retro–transposable elements. These diverse fusion sequences expanded the genome-targeting spectrum of MLT2A1 RNAs. Nevertheless, the shared MLT2A1 sequences partnered with heterogeneous nuclear ribonucleoprotein U (HNRNPU) to recruit RNA polymerase II, promoting global transcription of ZGA genes and autoamplification of the MLT2A1 subfamily. Thus, MLT2A1 chimeric RNAs formed an interlocking network that acts synergistically to boost human ZGA and early embryogenesis.
DOI: adv5257
Source: https://www.science.org/doi/10.1126/science.adv5257