Cells resist starvation through a nutrient stress splice switch.

Introns are common features of eukaryotic genes, typically removed through splicing to produce functional RNAs. In yeast, some introns play roles beyond host gene expression, mediating cellular responses to nutrient depletion. However, the mechanisms underlying these functions remain unclear. Here, we show that intron-dependent resistance to starvation is mediated by changes in spliceosome stoichiometry driven by a differential increase in the abundance of U1 small nuclear ribonucleoprotein (snRNP). Increased levels of U1 snRNP enhance its binding to, and promote splicing of, introns needed for improved tolerance to starvation. Nutrient depletion both increases and decreases the removal of different sets of introns. Remarkably, only introns that are more efficiently spliced out under starvation conditions are essential for resisting starvation. By investigating the mechanism using immunoprecipitation assays of different spliceosomal components, we found that the two sets of introns are differentially bound by U1 snRNP: starvation-induced introns are highly bound by U1, whereas underspliced introns bind less U1 snRNP in nutrient-limited conditions. Consistently, disrupting U1 interactions by mutating the 5' splice site or deleting nonessential U1 components significantly impairs starvation tolerance. These findings reveal a spliceosome-driven mechanism in which selective U1 recruitment to specific introns adapts cells to nutrient stress.