Role of NAT10-mediated RNA acetylation in premature ovarian insufficiency: a mechanistic review

Premature ovarian insufficiency (POI) is a multifactorial disease characterized by premature depletion of ovarian follicles, leading to impaired ovarian function and increased risk of systemic diseases such as osteoporosis and cardiovascular disease. Although POI significantly impacts women's reproductive health and increases the risk of systemic diseases, little is known about its potential mechanisms, which limits early diagnosis and treatment options. <i>N</i>-acetyltransferase 10 (NAT10), a key regulator of RNA acetylation, plays a crucial role in gene expression, cellular homeostasis, and stress response. This review explores the role of NAT10 in POI, emphasizing its involvement in cell apoptosis, autophagy, ferroptosis, inflammation, oxidative stress, and oocyte maturation disorders. Evidence reveals the dual role of NAT10 in regulating cell damage, balancing protective antioxidant defense and pro-apoptotic/inflammatory pathways depending on the cellular context. Dysregulation of NAT10 suggests its potential utility as a biomarker for early POI diagnosis. Furthermore, NAT10 inhibitors such as Remodelin may reduce ovarian cell damage by modulating apoptosis, inflammation, and oxidative stress. While these findings highlight NAT10 as a promising diagnostic and therapeutic target, challenges remain due to the complexity of its mechanisms and the need for more specific inhibitors. Translating these insights into clinical practice requires integrating molecular and clinical research to refine NAT10-based strategies. This review underscores the pivotal role of NAT10 in the pathophysiology of POI, paving the way for precision medicine and novel therapies targeting NAT10 to address ovarian dysfunction.