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Pharmacological Depletion of Polyamines with DFMO in Neuroblastoma cell line SKNBE2

GSE301290 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/01/22 Platform GPL24676
Summary
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 pre-mRNA splicing. We find that the inhibition of polyamine synthesis increases the phosphorylation of spliceosomal proteins, concomitant with remarkable perturbation of alternative splicing in cells and tissues. Mechanistically, molecular modeling together with biochemical assays revealed that polyamines bind to acidic phosphorylatable motifs in splicing factors of the U2 snRNP SF3 subcomplex, thus preventing the action of kinases. The molecular process through which polyamines regulate protein phosphorylation is a phenomenon that we define as “metabolic shielding”.
Published in
Polyamine-dependent metabolic shielding regulates alternative splicing
Zabala-Letona A, Pujana-Vaquerizo M, Martinez-Laosa B et al. · Nature 2026 · PMID 41535471 · doi:10.1038/s41586-025-09965-1
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Also filed as BioProject PRJNA1284761 and SRA study SRP596377. Searching any of these in the dataset finder brings you back here.

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