NGS analysis of WT and snf2∆ transcriptomes

Despite its streamlined genome, there are important examples of regulated RNA splicing in Saccharomyces cerevisiae. One of the most striking is the regulated splicing of meiotic transcripts, part of the dramatic reprogramming of gene expression upon meiotic onset. Here we show a crucial role for the chromatin remodeler Snf2, part of the Swi/Snf complex in meiotic regulation of splicing. We find that the complex affects meiotic splicing in several ways. First, meiosis-specific expression of the splicing activator Mer1 is Swi/Snf dependent, involves precise timing of acetylation of histone H3K9 at the MER1 locus, and changes in the acetylation state of Snf2. Additionally, Swi/Snf abundance regulates meiosis-specific downregulation of ribosomal protein encoding RNAs, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs to meiotic transcripts. This regulation is achieved by rapid downregulation of the Snf2 protein. Taken together these data reveal that the Swi/Snf complex coordinates a cascade of events to direct the regulated splicing of meiotic genes, establishing it as a master regulator of meiotic splicing in S. cerevisiae.尽管酿酒酵母（Saccharomyces cerevisiae）拥有精简的基因组，但其中仍存在若干受调控的RNA剪接（RNA splicing）重要实例。其中最引人注目的案例之一为减数分裂转录本（meiotic transcripts）的调控剪接，这是减数分裂启动时基因表达剧烈重编程的组成部分。本研究揭示了染色质重塑因子（chromatin remodeler）Snf2——Swi/Snf复合物（Swi/Snf complex）的核心组分——在减数分裂剪接调控中的关键作用。我们发现该复合物通过多种途径影响减数分裂剪接：其一，剪接激活因子（splicing activator）Mer1的减数分裂特异性表达依赖于Swi/Snf复合物，该过程涉及MER1基因座处组蛋白H3K9乙酰化（histone H3K9 acetylation）的精准时序调控，以及Snf2自身乙酰化状态的改变。此外，Swi/Snf复合物的丰度可调控编码核糖体蛋白的RNA（ribosomal protein encoding RNAs）发生减数分裂特异性下调，进而促使剪接体（spliceosomes）从这类高丰度含内含子RNA（intron-containing RNAs）类群重新分布至减数分裂转录本。该调控效应通过Snf2蛋白的快速下调得以实现。综合上述数据可见，Swi/Snf复合物可协调一系列级联事件，以指导减数分裂基因的调控剪接，从而确立其作为酿酒酵母（S. cerevisiae）减数分裂剪接主调控因子（master regulator）的核心地位。