Extended Data Fig. 6: Effects of uORF expression on downstream ORF translation, Related to Fig. 6.
From: Developmental dynamics of RNA translation in the human brain
(a) Scatterplot of fold-changes in translation between adult and prenatal brain for sORFs and canonical ORFs expressed from the same transcript. Positive values indicate enrichment in the adult brain, whereas negative values indicate enrichment in the prenatal brain. Red points indicate genes where sORF translation is significantly (DESeq2 padj < 0.05) enriched in prenatal brain while canonical ORF translation is significantly (DESeq2 padj < 0.05) enriched in adult brain. Blue points indicate genes where sORF translation is significantly (DESeq2 padj < 0.05) enriched in adult brain while canonical ORF translation is significantly (DESeq2 padj < 0.05) enriched in prenatal brain. While most sORFs exhibited concordant translation with their associated canonical ORFs across development, we identified 50 sORFs that were discordant with nearby canonical ORF translation, and these discordant sORFs were strongly enriched for uORFs translated from 5′UTRs of annotated protein-coding genes. (b) Stacked bar plot of numbers and percentages of sORFs detected in human brain (all sORFs), or sORFs exhibiting oppositely regulated expression across development compared to a canonical ORF translated from the same gene, separated by sORF type. (c) Scatterplot of fold-changes in translation between adult and prenatal brain for sORFs and canonical ORFs expressed from the same transcript, separated by type of ORF. Positive values indicate enrichment in the adult brain, whereas negative values indicate enrichment in the prenatal brain. Red points indicate genes where sORF translation is significantly (DESeq2 padj < 0.05) enriched in prenatal brain whereas canonical ORF translation is significantly (DESeq2 padj < 0.05) enriched in adult brain. Blue points indicate genes where sORF translation is significantly (DESeq2 padj < 0.05) enriched in adult brain whereas canonical ORF translation is significantly (DESeq2 padj < 0.05) enriched in prenatal brain. (d) Genomic locus of DLGAP1. Tracks represent merged and depth-normalized reads across all adult vs. prenatal samples for RNA-seq, Ribo-seq, as well as P-site positions. The sORF identified by RibORF is shown in gold.
