Fig. 5
Gene length and a lower U1/PAS ratio predispose DDR genes to PCPA. a GO enrichment analysis of the 809 genes that underwent PCPA (FDR < 0.01) based on TT-seq analysis of cells treated with THZ531 (400 nM for 2 h). b Box plots and bar plots showing the distribution and numbers of PCPA and DDR genes in the different gene-length categories established in Fig. 2d (****p < 0.0001, **p < 0.01, Fisher’s exact test). The center line indicates the median for each data set. c TT-seq and poly(A) 3′-seq tracks at the BLM DDR gene locus depicting the loss of annotated terminal polyadenylation signal and the presence of early termination due to PCPA in cells treated with THZ531 as in a. d Number of intronic poly(A) sites as a function of transcript length. A polynomial regression curve is plotted for all genes (black) and DDR genes only (red) (p = 1.7e−13, predicted vs. observed, Wilcoxon rank-sum test). e Box plots comparing the indicated determinants of PCPA in all genes vs. PCPA genes only and the proportion of DDR genes within the latter subset (see figure for p and d values; Wilcoxon rank-sum test & Cohen’s d effect-size, respectively). The black and red center lines indicate the median of all PCPA and DDR genes respectively. f Cumulative fraction plot showing the change in expression of PCPA (p = 2.2e−16, Kolmogorov-Smirnov test) and DDR (p = 1.9e−14, Kolmogorov-Smirnov test) transcripts relative to other transcripts following THZ531 treatment as in a
