An Ke, Liu Ruijuan, Yang Han, Feng Luyao, Zhang Xinhan, Zhang Xuran, Hou Mingyang, Wei Jingyao, Han Xiao, Shi Boyang, Yao Huan, Chen Xing, Wang Han, Tian Xin
Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, 450052, China.
Sci China Life Sci. 2025 Jun 23. doi: 10.1007/s11427-024-2841-x.
5-methylcytosine (mC) is a prevalent RNA modification that has various impacts on mRNA fate. Here, we generated 30 single-base resolution RNA mC methylomes and revealed the dynamic nature of mC of heart, muscle, lung, esophagus, stomach, pancreas, colon, jejunum, and rectum from 7 adult human individuals using RNA-BisSeq. Based on clustering analysis, the heart and muscle formed one cluster, while the remaining tissues constituted another cluster. Intriguingly, we observed a discrepancy pattern between mC levels and gene expression in these tissues when comparing the mC methylome and transcriptome. Moreover, we identified differences in NSUN2-mediated mC modifications between esophageal paracancerous tissues and healthy individual tissues. Notably, NSUN2 was found to interact with PLXNA1 mRNA, and silencing NSUN2 in esophageal squamous cell carcinoma (ESCC) cells resulted in the downregulation of PLXNA1 expression through an mC-mediated mechanism. Overall, our study provides valuable insights into the mC profile and the relationship between the methylome and transcriptome in human tissues, highlighting the potential role of mC modification as an epitranscriptomic biomarker.
5-甲基胞嘧啶（mC）是一种普遍存在的RNA修饰，对mRNA的命运有着多种影响。在此，我们生成了30个单碱基分辨率的RNA mC甲基化组，并使用RNA-BisSeq揭示了7名成年人类个体的心脏、肌肉、肺、食管、胃、胰腺、结肠、空肠和直肠中mC的动态特性。基于聚类分析，心脏和肌肉形成一个聚类，而其余组织构成另一个聚类。有趣的是，在比较mC甲基化组和转录组时，我们在这些组织中观察到mC水平与基因表达之间的差异模式。此外，我们确定了食管旁癌组织与健康个体组织之间NSUN2介导的mC修饰差异。值得注意的是，发现NSUN2与PLXNA1 mRNA相互作用，并且在食管鳞状细胞癌（ESCC）细胞中沉默NSUN2会通过mC介导的机制导致PLXNA1表达下调。总体而言，我们的研究为人类组织中的mC图谱以及甲基化组与转录组之间的关系提供了有价值的见解，突出了mC修饰作为一种表观转录组学生物标志物的潜在作用。
