Stm1 regulates Ifh1 activity revealing crosstalk between ribosome biogenesis and ribosome dormancy

Abstract

Nutrient abundance boosts ribosome biogenesis, whereas ribosome dormancy factors limit ribosome degradation upon starvation. The equilibrium between the two pathways governs cell growth. In this study, we identified suppressor of Tom1 (Stm1) as a molecular link between ribosome protection and biogenesis in Saccharomyces cerevisiae. While Stm1 was previously described as a dormancy factor, we show that it activates Ifh1, a transcriptional activator of ribosomal protein genes. Stm1 transiently localizes to the nucleolus, where it interacts with pre-ribosomes and directly binds RNA and Ifh1 through its C-terminal intrinsically disordered region (IDR). Although the IDR is dispensable for ribosome protection, its loss compromises cell growth. The IDR is phosphorylated upon nutrient starvation, which disrupts its interaction with Ifh1. Our findings reveal a molecular pathway sensing and adjusting ribosome abundance in response to nutrient availability, reinforcing the relevance of regulated ribosome homeostasis in physiology and disease.

Keywords: Ifh1; RGG/GAR motif; RNA-binding; RPG transcription; Stm1; homeostasis; ribosome; ribosome biogenesis; ribosome degradation; ribosome dormancy.