Liu Yan-Na, Li Ke-Yi, Wei Hao, Li Wen-Xiu, Zhang Yue-Hua, Qiu Jia-Jun, Zeng Fanyi, Yan Jing-Bin
Shanghai Children's Hospital, Shanghai Institute of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200040, China.
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, 200030, China.
BMC Genomics. 2025 Jul 1;26(1):600. doi: 10.1186/s12864-025-11807-3.
The maternal-to-zygotic transition (MZT) is a critical process in early human development, involving the degradation of maternal gene transcripts and activation of zygotic genes. Any disruption in the degradation of maternal transcripts may be associated with some reproductive disorders. However, the precise mechanism by which maternal gene transcripts are degraded during this transition remains unclear.
Through an analysis of weighted gene co-expression networks, an oocyte-specific module was identified, showing high consistency with the expression pattern of maternal transcripts degraded at the 8-cell stage, which is associated with the cell cycle and transcription factor binding. Within this module, a maternal long non-coding RNA known as OIP5 antisense RNA 1 (OIP5-AS1) was identified. It was observed that OIP5-AS1 can bind to the RNA binding protein human antigen R (HuR), potentially limiting its availability for other mRNAs and contributing to the degradation of maternal transcripts during MZT. Moreover, RNA immunoprecipitation sequencing in human induced pluripotent stem cells (iPSCs) revealed HuR and OIP5-AS1 are likely to tightly bind together and involved in functions related to the cell cycle and transcriptional regulation. Upon knocking down OIP5-AS1 and the ELAVL1 gene, which encodes the HuR protein in human iPSCs, a significant reduction in the expression levels of maternal transcripts was observed, suggesting an essential role of these factors in regulating maternal transcript stability during early development.
The HuR protein plays a critical role in influencing the degradation of maternal transcripts during the MZT in early human embryonic development. Understanding the role of OIP5-AS1 in regulating HuR protein could provide valuable insights into developmental biology and potentially lead to new therapeutic strategies for developmental disorders.
母源-合子转变（MZT）是人类早期发育中的一个关键过程，涉及母源基因转录本的降解和合子基因的激活。母源转录本降解过程中的任何破坏都可能与一些生殖障碍有关。然而，在此转变过程中母源基因转录本被降解的确切机制仍不清楚。
通过对加权基因共表达网络的分析，鉴定出一个卵母细胞特异性模块，其与在8细胞期降解的母源转录本的表达模式高度一致，这与细胞周期和转录因子结合有关。在该模块中，鉴定出一种名为OIP5反义RNA 1（OIP5-AS1）的母源长链非编码RNA。观察到OIP5-AS1可以与RNA结合蛋白人类抗原R（HuR）结合，可能会限制其对其他mRNA的可用性，并有助于在MZT期间母源转录本的降解。此外，人类诱导多能干细胞（iPSC）中的RNA免疫沉淀测序显示HuR和OIP5-AS1可能紧密结合在一起，并参与与细胞周期和转录调控相关的功能。在人类iPSC中敲低OIP5-AS1和编码HuR蛋白的ELAVL1基因后，观察到母源转录本的表达水平显著降低，表明这些因子在早期发育过程中调节母源转录本稳定性方面起着重要作用。
HuR蛋白在人类早期胚胎发育的MZT过程中对母源转录本的降解起着关键作用。了解OIP5-AS1在调节HuR蛋白中的作用可为发育生物学提供有价值的见解，并可能为发育障碍带来新的治疗策略。
