Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Genetics. 2023 Dec 6;225(4). doi: 10.1093/genetics/iyad163.
Across eukaryotic genomes, multiple α- and β-tubulin genes require regulation to ensure sufficient production of tubulin heterodimers. Features within these gene families that regulate expression remain underexplored. Here, we investigate the role of the 5' intron in regulating α-tubulin expression in Saccharomyces cerevisiae. We find that the intron in the α-tubulin, TUB1, promotes α-tubulin expression and cell fitness during microtubule stress. The role of the TUB1 intron depends on proximity to the TUB1 promoter and sequence features that are distinct from the intron in the alternative α-tubulin isotype, TUB3. These results lead us to perform a screen to identify genes that act with the TUB1 intron. We identified several genes involved in chromatin remodeling, α/β-tubulin heterodimer assembly, and the spindle assembly checkpoint. We propose a model where the TUB1 intron promotes expression from the chromosomal locus and that this may represent a conserved mechanism for tubulin regulation under conditions that require high levels of tubulin production.
在真核生物基因组中,多个α-和β-微管蛋白基因需要调节以确保微管蛋白异二聚体的足够产生。调节这些基因家族表达的特征仍未得到充分探索。在这里,我们研究了 5' 内含子在调节酿酒酵母中α-微管蛋白表达中的作用。我们发现,α-微管蛋白 TUB1 中的内含子在微管蛋白应激期间促进α-微管蛋白表达和细胞适应性。TUB1 内含子的作用取决于与 TUB1 启动子的接近程度和与替代α-微管蛋白同工型 TUB3 的内含子不同的序列特征。这些结果促使我们进行了一项筛选,以鉴定与 TUB1 内含子相互作用的基因。我们鉴定了几个参与染色质重塑、α/β-微管蛋白异二聚体组装和纺锤体组装检查点的基因。我们提出了一个模型,即 TUB1 内含子促进来自染色体基因座的表达,这可能代表在需要高水平微管蛋白产生的条件下调节微管蛋白的保守机制。