High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis.
High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis.
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DOI：
10.1016/j.cell.2013.10.047
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发表时间：
2013-12-05
期刊：
影响因子：
64.5
通讯作者：
Regev A
中科院分区：
文献类型：
--
作者：
Schwartz S;Agarwala SD;Mumbach MR;Jovanovic M;Mertins P;Shishkin A;Tabach Y;Mikkelsen TS;Satija R;Ruvkun G;Carr SA;Lander ES;Fink GR;Regev A
N6 - 甲基腺苷（m6A）是最普遍的信使核糖核酸（mRNA）碱基修饰，但对其精确位置、时间动态和调控知之甚少。在此，我们以近乎单核苷酸的分辨率绘制了减数分裂酵母转录本中m6A位点的基因组图谱，在1183个转录本中确定了1308个可能的甲基化位点。我们通过直接的遗传学分析验证了不同基因中的8个甲基化位点，证明了甲基化位点在一个相关物种中具有显著的保守性，并建立了一个可直接根据序列预测甲基化位点的模型。这些位点在密集的减数分裂时间进程中的甲基化情况各不相同，并且既在局部通过每个位点可预测的甲基化能力进行调控，也在整体上通过核心减数分裂回路进行调控。甲基转移酶复合物成分定位于酵母核仁，这种定位对mRNA甲基化至关重要。我们的数据阐明了酵母减数分裂中一个保守的、动态调控的甲基化程序，并为研究这种表观转录组修饰的功能提供了重要资源。
N6-methyladenosine (m6A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m6A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated 8/8 methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time-course, and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminates a conserved, dynamically regulated methylation program in yeast meiosis, and provides an important resource for studying the function of this epitranscriptomic modification.
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