血管衰老过程中NSUN2与METTL3/METTL14对衰老相关基因mRNA的协同甲基化以及血清m6A与m5C水平分析

RNA 甲基化是细胞衰老与血管炎症的重要调控因素，但在血管衰老性病理过程中的意义尚待探讨。前期研究发现：1）NSUN2与METTL3/METTL14 (分别催化m5C与m6A甲基化) 协同甲基化许多衰老或血管病理相关mRNA； 2）高脂饮食诱导血管NSUN2、METTL3及METTL14表达；3）血清RNA m5C与m6A水平在高脂饮食小鼠升高但在衰老小鼠降低；4）血清RNA m5C与m6A水平在高脂血症人群有升高趋势，但在衰老人群则有降低趋势。本课题将进一步探讨NSUN2与METTL3/METTL14协同甲基化衰老相关基因mRNA并调控其表达的机制，探讨这些调控过程在血管衰老及相关病理过程中的意义，探讨血清RNA （或特定RNA）m5C与m6A水平是否可作为衰老及相关血管病理改变的标志。 这些研究将从新角度解析衰老与相关血管病理改变的机理，也将对RNA甲基化基础研究成果进行临床转化尝试。

RNA methylation is important for the gene regulation in cellular aging and vascular inflammation. However, the impact of RNA methylation in vascular aging and aging-related vascular disorders remain to be further studied. In previous study, we have found that: 1) NSUN2 and METTL3/METTL14 cooperatively methylate a lot of common target mRNAs encoding aging- or vascular disease-related factors for methylation; 2) the expression of NSUN2, METTL3, and METTL14 and vascular tissues could be induced by high-fat diet; 3) serum m5Cand m6A increased in high-fat diet mice but deceased in aged mice；4) The levels of m5C and m6A increased in Hyperlipidemia population, but decreased in aged population. Based on these findings, we set out to investigate the role of NSUN2- and METTL3/METTL14-mediated mRNA methylation in the regulation of aging-related genes and the mechanisms underlying these regulation, to investigate the impacts of NSUN2- and METTL3/METTL14-mediated mRNA methylation in vascular aging and aging-related vascular disorders, and to investigate whether serum RNA m5C and m6A levels could be used as a marker for aging and the aging-related vascular disorders. Our study will further reveal the mechanisms underlying aging and aging-related vascular disorders. Furthermore, these studies will be helpful for the pursuit of the current achievement in the area of RNA methylation toward clinical translational studies.