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.通过剪接（splicing）过程从编码基因（coding gene）中切除内含子（intron），是所有真核生物（eukaryote）共有的普遍特征。本研究表明，通过改变剪接体（spliceosome）组分的化学计量比，实现剪接程序的全局重塑，是细胞抵抗饥饿的关键介导因子。转录组学（transcriptomics）与遗传分析显示，营养匮乏会通过不对称提升U1小核蛋白复合物（U1 small nuclear protein complex）的丰度，重构剪接程序，使其优先剪接减数分裂基因（meiotic gene），并抑制核糖体蛋白基因（ribosomal protein gene）的剪接。削弱U1与剪接位点（splice site）的结合，会改变剪接程序中依赖营养的变化模式，进而提升细胞对饥饿的敏感性。本研究揭示了一种全新的机制：细胞可通过改变剪接体组分的化学计量比，重编程剪接体的剪接偏好性，从而抵抗饥饿。