Replicative aging in yeast involves dynamic intron retention patterns associated with mRNA processing/export and protein ubiquitination.

IF 4.1 3区 生物学 Q2 CELL BIOLOGY Microbial Cell Pub Date : 2024-02-23 eCollection Date: 2024-01-01 DOI:10.15698/mic2024.02.816
Jesús Gómez-Montalvo, Alvaro de Obeso Fernández Del Valle, Luis Fernando De la Cruz Gutiérrez, Jose Mario Gonzalez-Meljem, Christian Quintus Scheckhuber
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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.

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酵母的复制衰老涉及与 mRNA 处理/输出和蛋白质泛素化相关的动态内含子保留模式。
面包酵母(Saccharomyces cerevisiae)对机体衰老的一些基本机制产生了相关的认识。其中包括基因组不稳定性、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寿命短或寿命长的表型。致力于揭示潜在细胞机制的研究可以帮助确定其他物种的衰老保守机制。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调节其基因表达。据我们所知,我们首次研究了酵母菌复制衰老过程中的替代剪接,尤其是内含子的保留。这是通过在 Janssens 等人(2015 年)之前发表的 RNA-seq 数据集上使用 IRFinder 算法实现的。在本研究中,我们在 43 个基因中发现了 44 个在复制衰老过程中不同程度保留的内含子。我们发现,内含子保留发生变化的基因在总体转录水平上并没有显示出显著的变化。我们可以从功能上将这些基因的不同组分配给早期和中期酵母的 mRNA 处理和输出(如 YRA1)以及老年细胞的蛋白质泛素化(如 UBC5)等细胞过程。总之,我们的研究揭示了酵母衰老转录程序中一个以前未曾探索过的层次,并从更广泛的意义上扩展了人们对面包酵母中发生的替代剪接的认识。
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来源期刊
Microbial Cell
Microbial Cell Multiple-
CiteScore
6.40
自引率
0.00%
发文量
32
审稿时长
12 weeks
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