Research Advances in m⁶A Methylation and Sepsis

Lifan Zhang^1,2Wenjuan Chen^1,2Yafeng Liu^1,2Shujun Zhang^1,2Bingyou Yin^1,2Kaijie Liu^1,2Xinyu Gu^3*Xinjun Hu^1,2*

• ¹Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
• ²Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology, Luoyang, China
• ³Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China

Sepsis is an infection-induced syndrome driven primarily by dysregulated host inflammatory responses. This process induces complex physiological changes that provoke systemic inflammation and multi-organ dysfunction, severely threatening survival in advanced cases.N6-methyladenosine (m⁶A), the most prevalent eukaryotic RNA modification, orchestrates crucial regulatory functions across biological processes and is a focal point in epigenetics. This modification is dynamically controlled by three protein classes: writers that catalyze m⁶A deposition, erasers that mediate its removal, and readers that decode modification signals. Substantial evidence implicates m⁶A dysregulation in sepsis-induced multi-organ damage, encompassing cardiovascular dysfunction, acute lung injury, and acute kidney injury. This review synthesizes current mechanistic insights into m⁶A's role in sepsis pathogenesis. By delineating how m⁶A governs inflammatory cascades and organ injury pathways, we evaluate its therapeutic targeting potential, providing translational frameworks for future research.