Fig. 5: Regulation of translation by polyamine depletion is driven by fractional codon content.
From: Reprogramming neuroblastoma by diet-enhanced polyamine depletion
a, Gene set enrichment analysis (GSEA) of protein biosynthesis using omics layers: gene-expression (RNA-seq), gene translation (Ribo-seq) and protein (proteomics) levels. GSEA compares ProArg-free plus DFMO to CD using the Reactome gene sets. All pathways are depicted, ranked by significance (Benjamini–Hochberg correction) and signed by normalized enrichment score (NES). The most downregulated and upregulated sets at the protein level are cell cycle and neuronal system, respectively. Lines connect gene sets across the omics layers. b, Mean fraction of codons with adenosine in the third position (A-ending codons) across all pathways and significantly changed pathways identified in a. Pathways taken from Reactome gene sets. c, The percentage of codons with adenosine in the third position correlates with the average protein level across Reactome pathways. Pathways with an increasing fraction of codons with adenosine in the third position have lower protein levels in ProArg-free DFMO compared with CD. FC, fold change. d, Fold change across omics layers of top downregulated cell cycle proteins indicates that differences between ProArg-free diet plus DFMO and CD occur predominantly on the protein level. e, Percentage of codons with the respective nucleotide at the third position in the Itgb3bp gene (encoding CENPR protein) compared with the transcriptome background. In a,c,d, RNA-seq, ProArg-free + DFMO: n = 5; CD: n = 4. Ribo-seq, n = 5. Proteomics, ProArg-free + DFMO: n = 6; CD: n = 5. Panels a and b created in BioRender. Morscher, R. (2025) https://BioRender.com/ygrgncb (a); https://BioRender.com/566gynw (b).
