脊髓损伤后缺血再灌注损伤（SCIRI）诱导脊髓神经元凋亡是阻碍神经功能修复的重要因素。课题组前期研究初步揭示RNA甲基转移酶、m6A修饰、circRNAs、m6A circRNAs在氧糖剥夺/再复氧模型脊髓神经元凋亡中的重要作用，筛选获得主要作用RNA甲基转移酶Mettl14，在此基础上：（1）CRISPR/Cas9技术制备Mettl14基因敲除小鼠，体内外系统研究Mettl14基因敲除调控脊髓神经元凋亡修复脊髓损伤；（2）甲基化RNA免疫共沉淀测序、翻译调控技术等明确Mettl14介导m6A修饰调控的circRNAs及其m6A修饰，确定关键circRNAs，解析m6A修饰调控circRNAs-miRNAs分子海绵机制及驱动circRNAs翻译机制。本研究可阐明RNA甲基转移酶Mettl14—m6A circRNAs—脊髓神经元凋亡的RNA表观遗传学调控机制，为脊髓损伤靶向治疗奠定基础。

Spinal cord neuron apoptosis induced by spinal cord ischemia-reperfusion injury (SCIRI) is an important factor hindering the neurological repair. The preliminary study of research group revealed an important role of RNA methyltransferase, m6A modification, circRNAs and m6A circRNAs in the apoptosis of spinal cord neuron in oxygen-glucose deprivation/reperfusion model, and screened out the RNA methyltransferase Mettl14 with vital regulatory functions. Based on previous study: (1) we will systematically research how Mettl14 knockout regulate spinal cord neuron apoptosis and repair spinal cord injury in vitro and in vivo with Mettl14 knockout mice prepared by CRISPR/Cas9 technology; (2) we will figure out circRNAs and m6A modifications modified by Mettl14-mediated m6A using MeRIP-Seq and translational regulation technology, identify the key circRNAs, and analyze the mechanism how m6A modification regulates circRNAs-microRNAs molecular sponges and drives circRNAs translation. The study will elucidate the RNA epigenetic regulation mechanism of RNA methyltransferase Mettl14-m6A circRNAs-spinal neuron apoptosis, which lays a foundation for targeted therapy of spinal cord injury.