Stanford Genome Technology Center, Department of Biochemistry, Stanford University School of Medicine, 855 California Ave., Palo Alto, California 94304, USA.
Genetics. 2009 Sep;183(1):185-94. doi: 10.1534/genetics.109.105155. Epub 2009 Jun 29.
It is well established that higher eukaryotes use alternative splicing to increase proteome complexity. In contrast, Saccharomyces cerevisiae, a single-cell eukaryote, conducts predominantly regulated splicing through retention of nonfunctional introns. In this article we describe our discovery of a functional intron in the PTC7 (YHR076W) gene that can be alternatively spliced to create two mRNAs that code for distinct proteins. These two proteins localize to different cellular compartments and have distinct cellular roles. The protein translated from the spliced mRNA localizes to the mitochondria and its expression is carbon-source dependent. In comparison, the protein translated from the unspliced mRNA contains a transmembrane domain, localizes to the nuclear envelope, and mediates the toxic effects of Latrunculin A exposure. In conclusion, we identified a definitive example of functional alternative splicing in S. cerevisiae that confers a measurable fitness benefit.
已有充分的证据表明,高等真核生物通过选择性剪接来增加蛋白质组的复杂性。相比之下,单细胞真核生物酿酒酵母主要通过保留无功能内含子来进行调控性剪接。在本文中,我们描述了在 PTC7(YHR076W)基因中发现的一个有功能的内含子,它可以通过选择性剪接产生两种编码不同蛋白质的 mRNA。这两种蛋白质定位于不同的细胞区室,具有不同的细胞功能。从剪接的 mRNA 翻译而来的蛋白质定位于线粒体,其表达依赖于碳源。相比之下,从未剪接的 mRNA 翻译而来的蛋白质含有一个跨膜结构域,定位于核膜,并介导 Latrunculin A 暴露的毒性作用。总之,我们在酿酒酵母中鉴定了一个明确的功能性选择性剪接的例子,这为其提供了可衡量的适应度优势。