RNA-m5C regulatory atlas of human fetal tissues uncover the activities of Nsun2/Jarid2/Alyref axis

作者：Xiujuan Hu, Chenyue Ding, Jiafeng Lu, Jincheng Li, Xiaolong Ren, Wenjuan Xia, Chunfeng Qian, Hong Li, Hoi‐Hung Cheung, Boxian Huang · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.08.004 · 被引用次数：5 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Epigenetics and DNA Methylation

• High levels of m5C methylation exist on mRNA of various organ tissues, especially brain tissues during the development of human fetus from early to middle pregnancy. • m5C modification is positively correlated with gene expression homeostasis, which involved in regulating the stability of fetal development. • Nsun2 cKO and Nsun5 KO reduce neuronal proliferation, increase apoptosis, affect m5C levels, neuronal maturation and DNA repair. • Nsun2-mediated the m5C modification of Jarid2 affects axonogenesis and forebrain development via regulating H3K27me3 and chromatin accessibility, regulating. • Alyref could assist the influencing consequences of Nsun2 loss via recognizing m5C modification on Jarid2/Ezh2. Cytosine methylation (m5C) is a pivotal RNA modification essential for human fetal development, yet its tissue-specific distribution and regulatory mechanisms remain largely undefined. This study aimed to construct a tissue-specific atlas of m5C distribution across human fetal tissues and to dissect the epigenetic crosstalk between RNA methylation and epigenetic regulation. Specifically, we focused on how Nsun2-mediated m5C modifications influence chromatin dynamics and histone modification patterns during fetal development. We performed RNA bisulfite sequencing (m5C-Seq) and transcriptome profiling (RNA-Seq) across seven distinct human fetal tissues. To explore the functional roles of m5C, we employed Nsun2 conditional knockout and Nsun5 knockout mouse models. We further i...