Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain.
Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain.
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DOI：
10.1186/s13059-016-1139-1
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发表时间：
2017-01-05
期刊：
影响因子：
12.3
通讯作者：
Lusser A
中科院分区：
文献类型：
--
作者：
Amort T;Rieder D;Wille A;Khokhlova-Cubberley D;Riml C;Trixl L;Jia XY;Micura R;Lusser A
最近的工作已经确定并绘制了一系列mRNA的转录后修饰，包括腺嘌呤中N6和N1位置的甲基化，假尿苷酸化和胞嘧啶（m5 C）中碳5的甲基化。然而，关于m5 C的流行和转录组分布的知识仍然非常有限;因此，需要在不同的细胞类型，组织和生物体中进行研究，以深入了解这种修饰的可能功能和对其他调控过程的影响。我们对小鼠胚胎干细胞和小鼠脑中总的和核的poly（A）RNA中的m5 C进行了无偏的全局分析。我们发现，有有趣的差异，在这些样品和细胞隔室的甲基化程度，甲基化的转录本的功能分类，和转录本内的位置偏差。具体而言，我们观察到m5 C位点在翻译起始密码子附近的显著积累，编码序列的消耗以及3′ UTR的混合富集模式。甲基化的程度和模式将胚胎干细胞和脑中修饰的转录物与任何一个样品中甲基化的转录物区分开来。我们还分析了m5 C和微小RNA靶位点，RNA结合蛋白的结合位点和N6-甲基腺苷之间的潜在相关性。我们的研究提出了第一个全面的图片胞嘧啶甲基化的表位转录组的多能和分化阶段的小鼠。这些数据为进一步研究m5 C在哺乳动物mRNA中的功能和生物学意义提供了宝贵的资源。本文的在线版本（doi：10.1186/s13059-016-1139-1）包含补充材料，可供授权用户使用。
Recent work has identified and mapped a range of posttranscriptional modifications in mRNA, including methylation of the N6 and N1 positions in adenine, pseudouridylation, and methylation of carbon 5 in cytosine (m5C). However, knowledge about the prevalence and transcriptome-wide distribution of m5C is still extremely limited; thus, studies in different cell types, tissues, and organisms are needed to gain insight into possible functions of this modification and implications for other regulatory processes. We have carried out an unbiased global analysis of m5C in total and nuclear poly(A) RNA of mouse embryonic stem cells and murine brain. We show that there are intriguing differences in these samples and cell compartments with respect to the degree of methylation, functional classification of methylated transcripts, and position bias within the transcript. Specifically, we observe a pronounced accumulation of m5C sites in the vicinity of the translational start codon, depletion in coding sequences, and mixed patterns of enrichment in the 3′ UTR. Degree and pattern of methylation distinguish transcripts modified in both embryonic stem cells and brain from those methylated in either one of the samples. We also analyze potential correlations between m5C and micro RNA target sites, binding sites of RNA binding proteins, and N6-methyladenosine. Our study presents the first comprehensive picture of cytosine methylation in the epitranscriptome of pluripotent and differentiated stages in the mouse. These data provide an invaluable resource for future studies of function and biological significance of m5C in mRNA in mammals. The online version of this article (doi:10.1186/s13059-016-1139-1) contains supplementary material, which is available to authorized users.