Abstract:
Saccharomyces cerevisiae (baker\'s yeast) has yielded relevant insights into some of the basic mechanisms of organismal aging. Among these are genomic instability, oxidative stress, caloric restriction and mitochondrial dysfunction. Several genes are known to have an impact on the aging process, with corresponding mutants exhibiting short- or long-lived phenotypes. Research dedicated to unraveling the underlying cellular mechanisms can support the identification of conserved mechanisms of aging in other species. One of the hitherto less studied fields in yeast aging is how the organism regulates its gene expression at the transcriptional level. To our knowledge, we present the first investigation into alternative splicing, particularly intron retention, during replicative aging of S. cerevisiae. This was achieved by utilizing the IRFinder algorithm on a previously published RNA-seq data set by Janssens et al. (2015). In the present work, 44 differentially retained introns in 43 genes were identified during replicative aging. We found that genes with altered intron retention do not display significant changes in overall transcript levels. It was possible to functionally assign distinct groups of these genes to the cellular processes of mRNA processing and export (e.g., YRA1) in early and middle-aged yeast, and protein ubiquitination (e.g., UBC5) in older cells. In summary, our work uncovers a previously unexplored layer of the transcriptional program of yeast aging and, more generally, expands the knowledge on the occurrence of alternative splicing in baker\'s yeast.
摘要:
酿酒酵母(面包酵母)已经对生物体老化的一些基本机制产生了相关的见解。其中包括基因组不稳定,氧化应激,热量限制和线粒体功能障碍。已知有几个基因对衰老过程有影响,相应的突变体表现出短期或长期的表型。致力于揭示潜在细胞机制的研究可以支持对其他物种衰老的保守机制的识别。迄今为止,酵母衰老研究较少的领域之一是生物体如何在转录水平上调节其基因表达。据我们所知,我们提出了对选择性剪接的第一个研究,特别是内含子保留,在酿酒酵母的复制性老化过程中。这是通过在Janssens等人先前发表的RNA-seq数据集上利用IRFinder算法来实现的。(2015)。在目前的工作中,在复制衰老过程中,鉴定了43个基因中44个差异保留的内含子。我们发现内含子保留改变的基因在整体转录水平上没有显示出显著的变化。可以在功能上将这些基因的不同组分配给mRNA加工和输出的细胞过程(例如,YRA1)在早期和中期酵母中,和蛋白质泛素化(例如,UBC5)在较老的细胞中。总之,我们的工作揭示了酵母老化的转录程序的一个以前未探索的层,更一般地说,扩展了面包酵母中选择性剪接发生的知识。