Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston and University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030.
Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston and University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030
Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6808-E6816. doi: 10.1073/pnas.1801997115. Epub 2018 Jul 2.
Eukaryotes maintain fidelity of gene expression by preferential degradation of aberrant mRNAs that arise by errors in RNA processing reactions. In , Ski7 plays an important role in this mRNA quality control by mediating mRNA degradation by the RNA exosome. Ski7 was initially thought to be restricted to and close relatives because the gene and its paralog arose by whole genome duplication (WGD) in a recent ancestor. We have recently shown that the preduplication gene was alternatively spliced and that Ski7 function predates WGD. Here, we use transcriptome analysis of diverse eukaryotes to show that diverse eukaryotes use alternative splicing of to encode two proteins. Although alternative splicing affects the same intrinsically disordered region of the protein, the pattern of splice site usage varies. This alternative splicing event arose in an early eukaryote that is a common ancestor of plants, animals, and fungi. Remarkably, through changes in alternative splicing and gene duplication, the Ski7 protein has diversified such that different species express one of four distinct Ski7-like proteins. We also show experimentally that the gene has undergone multiple changes that are incompatible with the Hbs1 function and may also have undergone additional changes to optimize mRNA quality control. The combination of transcriptome analysis in diverse eukaryotes and genetic analysis in yeast clarifies the mechanism by which a Ski7-like protein is expressed across eukaryotes and provides a unique view of changes in alternative splicing patterns of one gene over long evolutionary time.
真核生物通过优先降解 RNA 加工反应错误产生的异常 mRNA 来维持基因表达的保真度。在 中，Ski7 通过介导 RNA 外切体对 mRNA 的降解，在这种 mRNA 质量控制中发挥重要作用。最初认为 Ski7 仅限于 及其近缘物，因为 基因及其旁系同源物 是在最近的祖先中通过全基因组复制（WGD）产生的。我们最近表明，前复制基因发生了选择性剪接，并且 Ski7 功能早于 WGD。在这里，我们使用不同真核生物的转录组分析来表明，不同的真核生物使用 基因的选择性剪接来编码两种蛋白质。尽管选择性剪接影响蛋白质的同一固有无序区域，但剪接位点的使用模式不同。这种选择性剪接事件发生在一个早期的真核生物中，它是植物、动物和真菌的共同祖先。值得注意的是，通过选择性剪接和基因复制的变化，Ski7 蛋白已经多样化，以至于不同的物种表达四种不同的 Ski7 样蛋白之一。我们还通过实验表明， 基因发生了多次与 Hbs1 功能不兼容的变化，并且可能还发生了其他变化以优化 mRNA 质量控制。在不同真核生物中的转录组分析和酵母中的遗传分析相结合，阐明了 Ski7 样蛋白在真核生物中表达的机制，并提供了一个独特的视角来看一个基因在漫长的进化时间内的选择性剪接模式变化。
