High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis

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. Examination of m6A methylation under various conditions

N6-甲基腺嘌呤（N6-methyladenosine，m6A）是真核生物信使RNA（messenger RNA，mRNA）中分布最为广泛的碱基修饰，但目前对其精准定位、时序动态及调控机制的认知仍较为有限。本研究构建了近乎单核苷酸分辨率的减数分裂酵母转录组内m6A位点的基因组图谱，在1183条转录本中共鉴定出1308个潜在甲基化位点。我们通过直接遗传分析验证了8个不同基因中的全部8个甲基化位点，证实甲基化位点在近缘物种中具有显著保守性，并搭建了可直接从序列信息预测甲基化位点的计算模型。不同位点的甲基化谱式在密集的减数分裂时间进程中呈现动态差异，其调控机制可分为两类：局部调控依赖于各位点自身的可甲基化特性，全局调控则通过核心减数分裂调控网络实现。甲基转移酶复合物的组分定位于酵母核仁，该定位对于mRNA的甲基化修饰至关重要。本研究的数据阐明了酵母减数分裂中一套保守且受动态调控的甲基化程序，同时为研究该表观转录组修饰的生物学功能提供了重要的资源。多种条件下的m6A甲基化检测