Venkataramanan Srivats, Douglass Stephen, Galivanche Anoop R, Johnson Tracy L
Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Nucleic Acids Res. 2017 Jul 27;45(13):7708-7721. doi: 10.1093/nar/gkx373.
Despite its relatively streamlined genome, there are important examples of regulated RNA splicing in Saccharomyces cerevisiae, such as splicing of meiotic transcripts. Like other eukaryotes, S. cerevisiae undergoes a dramatic reprogramming of gene expression during meiosis, including regulated splicing of a number of crucial meiosis-specific RNAs. Splicing of a subset of these is dependent upon the splicing activator Mer1. Here we show a crucial role for the chromatin remodeler Swi/Snf in regulation of splicing of meiotic genes and find that the complex affects meiotic splicing in two ways. First, we show that Swi/Snf regulates nutrient-dependent downregulation of ribosomal protein encoding RNAs, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs (the ribosomal protein genes) to Mer1-regulated transcripts. We also demonstrate that Mer1 expression is dependent on Snf2, its acetylation state and histone H3 lysine 9 acetylation at the MER1 locus. Hence, Snf2 exerts systems level control of meiotic gene expression through two temporally distinct mechanisms, demonstrating that it is a key regulator of meiotic splicing in S. cerevisiae. We also reveal an evolutionarily conserved mechanism whereby the cell redirects its energy from maintaining its translational capacity to the process of meiosis.
尽管酿酒酵母的基因组相对精简，但其中仍存在一些重要的RNA剪接调控实例，比如减数分裂转录本的剪接。与其他真核生物一样，酿酒酵母在减数分裂过程中会经历基因表达的剧烈重编程，包括对一些关键的减数分裂特异性RNA进行剪接调控。其中一部分RNA的剪接依赖于剪接激活因子Mer1。在此我们展示了染色质重塑因子Swi/Snf在减数分裂基因剪接调控中的关键作用，并发现该复合物通过两种方式影响减数分裂剪接。首先，我们发现Swi/Snf调控核糖体蛋白编码RNA的营养依赖性下调，从而导致剪接体从这类丰富的含内含子RNA（核糖体蛋白基因）重新分配至Mer1调控的转录本。我们还证明Mer1的表达依赖于Snf2、其乙酰化状态以及MER1基因座处组蛋白H3赖氨酸9的乙酰化。因此，Snf2通过两种时间上不同的机制对减数分裂基因表达进行系统水平的控制，表明它是酿酒酵母减数分裂剪接的关键调节因子。我们还揭示了一种进化上保守的机制，即细胞将其能量从维持翻译能力重新导向减数分裂过程。
