The origin and evolution of a distinct mechanism of transcription initiation in yeasts
The origin and evolution of a distinct mechanism of transcription initiation in yeasts
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DOI：
10.1101/2020.04.04.025502
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发表时间：
2020-04
期刊：
影响因子：
7
通讯作者：
Zhaolian Lu;Zhenguo Lin
中科院分区：
文献类型：
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作者：
Zhaolian Lu;Zhenguo Lin
RNA 聚合酶 II 转录的分子过程在真核生物中高度保守（“经典模型”）。有趣的是，在芽殖酵母酿酒酵母（“扫描模型”）中发现了一种定位转录起始位点（TSS）的独特方法。 “扫描模型”的起源及其潜在的遗传机制仍未解决。在这里，我们应用基因组方法来解决这些问题。我们首先使用 nAnT-iCAGE 技术以单核苷酸分辨率鉴定了 12 种酵母物种的 TSS，该技术通过提供准确的蛋白质编码基因 5' 边界，显着改善了这些基因组的注释。然后，我们根据物种的 TSS 图谱和基因组序列推断其启动机制。我们发现“扫描模型”起源于解脂耶氏酵母和其余芽殖酵母的分裂之后。在“扫描模型”物种的进化过程中，紧邻 TSS 上游的富含腺嘌呤的区域出现了，这可能有助于这些物种的 TSS 选择。两种起始机制都对 TSS 周围的嘧啶-嘌呤二核苷酸有强烈的偏好。我们的结果表明，嘌呤是准确招募第一个核苷酸所必需的，增加了 mRNA 成熟过程中被加帽的机会，这对于有效翻译起始至关重要。根据我们的发现，我们提出了“扫描模型”物种的 TSS 选择模型。此外，我们的研究还表明，内在序列特征主要决定了核心启动子（核心启动子形状）内起始活性的分布。
The molecular process of transcription by RNA Polymerase II is highly conserved among eukaryotes (“classic model”). Intriguingly, a distinct way of locating transcription start sites (TSSs) was found in a budding yeast Saccharomyces cerevisiae (“scanning model”). The origin of the “scanning model” and its underlying genetic mechanisms remain unsolved. Herein, we applied genomic approaches to address these questions. We first identified TSSs at a single-nucleotide resolution for 12 yeast species using the nAnT-iCAGE technique, which significantly improved the annotations of these genomes by providing accurate 5’boundaries of protein-coding genes. We then infer the initiation mechanism of a species based on its TSS maps and genome sequences. We found that the “scanning model” had originated after the split of Yarrowia lipolytica and the rest of budding yeasts. An adenine-rich region immediately upstream of TSS had appeared during the evolution of the “scanning model” species, which might facilitate TSS selection in these species. Both initiation mechanisms share a strong preference for pyrimidine-purine dinucleotides surrounding the TSS. Our results suggested that the purine is required for accurately recruiting the first nucleotide, increasing the chance of being capped during mRNA maturation, which is critical for efficient translation initiation. Based on our findings, we proposed a model of TSS selection for the “scanning model” species. Besides, our study also demonstrated that the intrinsic sequence feature primarily determines the distribution of initiation activities within a core promoter (core promoter shape).