Xie Yun, Zhou Chuanchuan, Guo Qi, Guo Yingchun, Guo Jiayi, Chen Lina, Liu Xiaoping, Zeng Yanyan, Liang Qiqi, Wu Taibao, Liu Jiawen, Liang Xiaoyan
Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
GuangDong Engineering Technology Research Center of Fertility Preservation, Guangzhou 510000, China.
Sci Adv. 2025 Jul 18;11(29):eadu0955. doi: 10.1126/sciadv.adu0955.
Patients with systemic lupus erythematosus (SLE) often have decreased fertility. Gene translation is crucial to oocyte meiosis and development. However, it remains unclear how SLE affects this process. Here, we used single-cell transcriptome and translatome sequencing to uncover a notable disruption in protein translation in oocytes from SLE mice, associated with the -acetylcytidine (acC) modification. Inhibition of acC levels in vitro substantially reduced oocyte translation efficiency. Notably, through trace-cell acC-RNA immunoprecipitation (acRIP) sequencing, we mapped the acC landscape in SLE mouse oocytes and found that deficient acC modification substantially impaired the translation of . Furthermore, we demonstrated that nicotinamide treatment notably and safely improved the quantity and quality of oocytes in SLE mice by enhancing acC modification levels. Our findings highlight the essential role of - acetyltransferase 10 (NAT10)-mediated acC modification in abnormal oocyte development in SLE and suggest that nicotinamide holds promise for improving fertility in patients with SLE.
系统性红斑狼疮（SLE）患者的生育能力往往会下降。基因翻译对卵母细胞减数分裂和发育至关重要。然而，SLE如何影响这一过程仍不清楚。在此，我们使用单细胞转录组和翻译组测序来揭示SLE小鼠卵母细胞中蛋白质翻译的显著破坏，这与N4-乙酰胞苷（acC）修饰有关。体外抑制acC水平可大幅降低卵母细胞翻译效率。值得注意的是，通过微量细胞acC-RNA免疫沉淀（acRIP）测序，我们绘制了SLE小鼠卵母细胞中的acC图谱，发现acC修饰缺陷会严重损害DDX4的翻译。此外，我们证明烟酰胺治疗通过提高acC修饰水平，显著且安全地改善了SLE小鼠卵母细胞的数量和质量。我们的研究结果突出了N4-乙酰转移酶10（NAT10）介导的acC修饰在SLE异常卵母细胞发育中的重要作用，并表明烟酰胺有望改善SLE患者的生育能力。
