Genome-wide identification of mRNA 5-methylcytosine in mammals
Genome-wide identification of mRNA 5-methylcytosine in mammals
复制标题
哺乳动物 mRNA 5-甲基胞嘧啶的全基因组鉴定
DOI：
10.1038/s41594-019-0218-x
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发表时间：
2019-05-01
影响因子：
16.8
通讯作者：
Zhang, Rui
中科院分区：
文献类型：
--
作者：
Huang, Tao;Chen, Wanying;Zhang, Rui
事实证明，在全转录组范围内准确、系统地检测 5-甲基胞嘧啶 (m5C) 具有挑战性，并且对于 mRNA 中这种修饰的普遍性存在相互矛盾的观点。在这里，我们报告了一个实验和计算框架，该框架使用一组高置信度位点可靠地识别 mRNA m5C 位点并确定与修饰相关的序列基序和结构特征。我们根据我们的框架开发了人类和小鼠组织中 RNA m5C 位点的定量图谱。在给定的组织中，我们通常会识别数百个外显子 m5C 位点。大约 62-70% 的位点具有低甲基化水平（<20% 甲基化），而 8-10% 的位点具有中度或高度甲基化（>40% 甲基化）。跨物种分析表明，甲基化水平的主要决定因素是物种，而不是组织类型，这表明 RNA 甲基化存在强顺式调控。综合起来，这些数据为识别 RNA 甲基化的调控和功能提供了宝贵的资源。
Accurate and systematic transcriptome-wide detection of 5-methylcytosine (m5C) has proved challenging, and there are conflicting views about the prevalence of this modification in mRNAs. Here we report an experimental and computational framework that robustly identified mRNA m5C sites and determined sequence motifs and structural features associated with the modification using a set of high-confidence sites. We developed a quantitative atlas of RNA m5C sites in human and mouse tissues based on our framework. In a given tissue, we typically identified several hundred exonic m5C sites. About 62–70% of the sites had low methylation levels (<20% methylation), while 8–10% of the sites were moderately or highly methylated (>40% methylation). Cross-species analysis revealed that species, rather than tissue type, was the primary determinant of methylation levels, indicating strongcis-directed regulation of RNA methylation. Combined, these data provide a valuable resource for identifying the regulation and functions of RNA methylation.