Wei Renyue, Yue Yanbin, Wu Yinhuan, Zhang Chenyuan, Jin Jun-Xue, Liu Zhonghua, Wang Jiaqiang
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China.
J Mol Cell Biol. 2025 Jun 28;17(1). doi: 10.1093/jmcb/mjae061.
The zygotic genome activation (ZGA) is crucial for the development of pre-implantation embryos. Long noncoding RNAs (lncRNAs) play significant roles in many biological processes, but the study on their role in the early embryonic development of pigs is limited. In this study, we identify lncFKBPL as an enhancer-type lncRNA essential for pig embryo development. lncFKBPL is expressed from the 4-cell stage to the morula stage in pig embryos, and interference with lncFKBPL leads to a developmental arrest at the 8-cell stage. Mechanistic investigations uncover that lncFKBPL is able to bind to MED8, thereby mediating enhancer activity and regulating FKBPL expression. Additionally, FKBPL interacts with the molecular chaperone protein HSP90AA1, stabilizing CDK9 and boosting its protein-level expression. Elevated CDK9 levels enhance Pol II phosphorylation, facilitating ZGA. Our findings illuminate the role of lncFKBPL as an enhancer lncRNA in pig ZGA regulation and early embryo development, providing a foundation for further exploration in this area.
合子基因组激活（ZGA）对于植入前胚胎的发育至关重要。长链非编码RNA（lncRNAs）在许多生物过程中发挥着重要作用，但关于它们在猪早期胚胎发育中的作用的研究有限。在本研究中，我们鉴定出lncFKBPL是一种对猪胚胎发育至关重要的增强子型lncRNA。lncFKBPL在猪胚胎中从4细胞阶段到桑椹胚阶段表达，干扰lncFKBPL会导致在8细胞阶段发育停滞。机制研究发现，lncFKBPL能够与MED8结合，从而介导增强子活性并调节FKBPL表达。此外，FKBPL与分子伴侣蛋白HSP90AA1相互作用，稳定CDK9并提高其蛋白水平表达。CDK9水平升高增强了Pol II磷酸化，促进了ZGA。我们的研究结果阐明了lncFKBPL作为增强子lncRNA在猪ZGA调控和早期胚胎发育中的作用，为该领域的进一步探索奠定了基础。
