Cells resist starvation through nutrients dependent splice switch

Removing introns from coding genes through the process of splicing is a ubiquitous feature of all eukaryotes. Here we show that global remodeling of splicing program through changing the stoichiometry of spliceosomal components is a key mediator of cell resistance to starvation. Transcriptomic and genetic analyses indicate that nutrients depletion reconfigures the splicing program to favor the splicing of meiotic genes and repress ribosomal protein genes by asymmetrically increasing the abundance of U1 small nuclear protein complex. Impairing U1 binding to splice site alters the nutrients dependent changes in the splicing program leading to increased sensitivity to starvation. This work reveals a new mechanism by which cells resist starvation through changes in the stoichiometry of the spliceosomal components and reprograming of the spliceosome splicing preference. To compare splicing genome wide using WT, nam8 deletion, and mud1 mutant strains in both log phase growth and nutrient depeletion/starvation conditions. This was done using Multiplexed Primer Extension Sequencing

通过剪接过程从编码基因中切除内含子，是所有真核生物的普遍特征。本研究证实，通过改变剪接体组分的化学计量比以全局重塑剪接程序，是细胞抵抗饥饿胁迫的关键介导因素。转录组学与遗传分析显示，营养耗竭可通过不对称提升U1小核蛋白复合物（U1 small nuclear protein complex）的丰度，重新配置剪接程序，优先剪接减数分裂基因并抑制核糖体蛋白基因的表达。破坏U1与剪接位点的结合，会改变营养依赖型的剪接程序变化，进而提升细胞对饥饿的敏感性。本研究揭示了一种全新的细胞抗饥饿机制：细胞通过改变剪接体组分的化学计量比并重编程剪接体的剪接偏好性，实现饥饿抵抗。为在对数生长期与营养耗竭/饥饿条件下，对野生型（WT）、nam8缺失菌株及mud1突变菌株开展全基因组范围的剪接比对分析，本研究采用了多重引物延伸测序（Multiplexed Primer Extension Sequencing）技术。