Alternative Splicing of RNA Triplets Is Often Regulated and Accelerates Proteome Evolution
Figure 1
Alternative splicing of tissue-specific NAGNAGs is highly conserved.
(A) Short reads were aligned to the intron-proximal and intron-distal splice junctions of NAGNAG splicing events in order to estimate isoform ratios. (B) Estimated proximal isoform usage (ψ) for a NAGNAG which inserts/deletes a predicted phosphorylation site in far upstream element binding protein 1 (FUBP1). Phosphorylation site and corresponding kinase were predicted by Scansite (Scansite z-score −3.024) [55]. Error bars indicate the 95% binomial confidence interval. (C) Number of reading frame-preserving alternative splicing events in protein-coding regions, with both isoforms expressed at ≥5% in at least one tissue (see also Table S1). (D) A NAGNAG which inserts/deletes an arginine in RNA recognition motif 4 (RRM4) of the splicing factor PTBP2 is deeply conserved. Alignment of orthologous 3′ splice site sequences shown below the NMR structure (PDB accession 2ADC, displayed with PyMOL) of the highly homologous PTBP1 protein (green) complexed with RNA (red) [33]. Boxed is K489 of PTBP1, which is homologous to the arginine shown in PTBP2, and hydrogen bonds to the RNA backbone (dotted yellow line). Putative branch point based on location of the first upstream AG, the sequence motif identified in [56], and the pattern of sequence conservation. (E) Conservation of alternative splicing between orthologous human and mouse NAGNAGs increases with tissue specificity. NAGNAGs that were alternatively spliced in human (left) and mouse (right) were grouped by switch score—defined as the maximum ψ difference between tissues—as indicated by colors, and the fraction of orthologs which were alternatively spliced in the other species is shown. Error bars indicate 95% binomial confidence intervals.
