Fig. 5
From: Discovery of physiological and cancer-related regulators of 3′ UTR processing with KAPAC
Regulation of PAS choice in glioblastoma samples from TCGA. a Cumulative distributions of weighted average length of 1172 terminal exons inferred by applying PAQR to five normal and five tumor samples (see “Methods” for the selection of these samples) show that terminal exons are significantly shortened in tumors. b Activity profile of CUCUCU, the second most significant motif associated with 3′ end processing changes in glioblastoma (number of PAS used in the inference n = 2119). The presence of the motif in a window from −25 to +75 relative to PAS is associated with increased processing of the site in normal tissue samples. c Expression of PTBP1 in the ten samples from a is strongly anti-correlated (dark colored points; Pearson’s r (rP) = −0.97, p value < 0.0001) with the median average length of terminal exons in these samples. In contrast, the expression of PTBP2 changes little in tumors compared to normal tissue samples, and has a positive correlation with terminal exon length (light colored points; rP = 0.85, p value = 0.002). d Position-dependent PTBP1 binding inferred from two eCLIP studies (in HepG2 (thick red line) and K562 (thick blue line) cell lines) by the ENCODE consortium is significantly enriched downstream of the 203 PAS predicted to be regulated by the CU-repeat motifs. We selected 1000 similar-sized sets of poly(A) sites with the same positional preference (distally located) as the targets of the CU motif and the density of PTBP1 eCLIP reads was computed as described in the “Methods” section. The mean and standard deviation of position-dependent read density ratios from these randomized data sets are also shown. e The median ratio of PTBP1-IP to background eCLIP reads over nucleotides 0 to 100 downstream of the PAS (position-wise ratios computed as in e), for the top 102 (top) and bottom 101 (low) predicted PTBP1 targets as well as for the background set (bg) of distal PAS. f Activity profile of the same CUCUCU motif in the PTBP1/2 double knock-down (where the motif ranked third) compared to control samples (two biological replicates from HEK cells, number of PAS n = 2493)