Diverse environmental stresses elicit distinct responses at the level of pre-mRNA processing in yeast
Diverse environmental stresses elicit distinct responses at the level of pre-mRNA processing in yeast
复制标题
DOI：
10.1261/rna.2754011
复制
发表时间：
2011-08-01
期刊：
影响因子：
4.5
通讯作者：
Guthrie, Christine
中科院分区：
文献类型：
--
作者：
Bergkessel, Megan;Whitworth, Gregg B.;Guthrie, Christine
真核细胞中的基因表达受到mRNAs转录后加工的深刻影响，包括内含子在核内的剪接以及细胞核和细胞质的降解途径。这些过程有可能影响含有内含子的转录本的稳态水平和变化的动力学。在这里，我们报告了使用剪接异构体特异的微阵列平台来研究不同的应激条件对前mRNA加工的影响。有趣的是，我们发现不同的压力会导致这一层面上的不同模式的变化。我们观察到的反应对RPG来说是最戏剧性的，可以分为三大类。第一种是RPG前体mRNA的积累，在多种类型的氨基酸饥饿机制中都可以看到；剪接抑制的程度与胁迫的严重程度有关。第二类的特征是前期和成熟的RPG mRNA迅速减少，并在许多胁迫中被看到，使TORC1激酶复合体失活。这些下降取决于含有内含子的前RNAs的核周转。第三类的特征是RPG前体mRNA的减少，只有成熟物种的RPG前mRNA略有减少；这种反应在高渗和阳离子毒性胁迫下观察到。我们表明，酪蛋白激酶2(CK2)在前mRNA处理的变化中做出了重要贡献，特别是在前两类应激反应中。总而言之，我们的数据表明，复杂的转录后程序协同微调含内含子的转录本在萌芽酵母中的表达。
Gene expression in eukaryotic cells is profoundly influenced by the post-transcriptional processing of mRNAs, including the splicing of introns in the nucleus and both nuclear and cytoplasmic degradation pathways. These processes have the potential to affect both the steady-state levels and the kinetics of changes to levels of intron-containing transcripts. Here we report the use of a splicing isoform-specific microarray platform to investigate the effects of diverse stress conditions on pre-mRNA processing. Interestingly, we find that diverse stresses cause distinct patterns of changes at this level. The responses we observed are most dramatic for the RPGs and can be categorized into three major classes. The first is characterized by accumulation of RPG pre-mRNA and is seen in multiple types of amino acid starvation regimes; the magnitude of splicing inhibition correlates with the severity of the stress. The second class is characterized by a rapid decrease in both pre- and mature RPG mRNA and is seen in many stresses that inactivate the TORC1 kinase complex. These decreases depend on nuclear turnover of the intron-containing pre-RNAs. The third class is characterized by a decrease in RPG pre-mRNA, with only a modest reduction in the mature species; this response is observed in hyperosmotic and cation-toxic stresses. We show that casein kinase 2 (CK2) makes important contributions to the changes in pre-mRNA processing, particularly for the first two classes of stress responses. In total, our data suggest that complex post-transcriptional programs cooperate to fine-tune expression of intron-containing transcripts in budding yeast.