Polyamine-dependent metabolic shielding regulates U2 snRNP SF3 subcomplex phosphorylation and alternative splicing

ABSTRACT: Metabolites are central to cellular homeostasis. Whereas much emphasis has been placed on their relevance to meet energetic and biosynthetic demands, metabolic intermediates also function as signaling molecules. Here we show that polyamines, small polycations that are essential for cell biology, regulate the process of alternative splicing. We find that inhibition of polyamine synthesis increases the phosphorylation of proteins belonging to the spliceosome, consistent with a remarkable perturbation of alternative splicing in cells and tissues. Mechanistically, polyamines bind to acidic phosphorylatable motifs in splicing factors of the U2 snRNP SF3 subcomplex, thus preventing the action of kinases. In summary, we report a molecular process through which polyamines regulate protein phosphorylation in a phenomenon that we define as metabolic shielding

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Pilar Ximenez-Embun  

LAB HEAD: Javier Muñoz

PROVIDER: PXD046107 | Pride | 2025-11-11

REPOSITORIES: Pride