Extended Data Fig. 8: Cross-RBP splicing maps.

a, Similar to Extended Data Fig. 6a, knockdown-altered skipped exons were identified for each RNA-seq experiment. However, for this analysis, normalized eCLIP read density at skipped exons that were excluded (left) or included (right) upon RBP knockdown versus nSEs was calculated separately for all RBPs within the same RBP class (identified in Fig. 2a). The heatmap then indicates the difference between the normalized eCLIP signal for the shRNA-targeted RBP and the mean of the normalized eCLIP signal for all other RBPs within that class. Shown are all 92 pairings of RBPs with eCLIP and KD–RNA-seq data and at least 100 included or excluded altered events, with hatching indicating data sets with fewer than 100 significantly altered events. b, Heatmap indicates normalized eCLIP signal at 492 HNRNPC knockdown-induced exons in HepG2 cells relative to nSEs for HNRNPC (top) and all other RBPs within the same binding class and cell type (bottom). c, As in b, for 138 RBFOX2 knockdown-excluded exons in HepG2 cells (as shown in Fig. 5d, but including all labels). d, Points indicate average change in ΔΨ in two replicates of RBFOX2 knockdown (x-axis) and QKI knockdown (y-axis) in HepG2 cells. Shown are 93 exons that were significantly altered (P < 0.05, FDR < 0.1, and |ΔΨ| > 0.05) from rMATS analysis of either RBFOX2 or QKI, and had at least 30 inclusion or exclusion reads in both replicates and average |ΔΨ| > 0.05 for both RBFOX2 and QKI knockdown. Significance was determined from correlation in MATLAB. e, For each of 138 RBFOX2 knockdown-excluded skipped exons in HepG2 cells, points indicate normalized RBFOX2 eCLIP enrichment at the +60 nt position of the downstream intron (x-axis) versus normalized QKI eCLIP enrichment at the +150 nt position of the downstream intron (y-axis). f, As in b, for 160 TIA1 knockdown-included exons in HepG2 cells. Right, black indicates mean of 15 non-TIA1 data sets in the same binding class, with the 10th–90th percentiles indicated in grey. g, Western blot for (left) TIAL1 and (right) TIA1 of IP performed with IgG, TIA1 (RN014P, MBLI), and TIAL1 (RN059PW, MBNL) primary antibodies. This experiment was performed once. h, As in d, for TIA1 and TIAL1 at 107 TIA1 knockdown-included exons in HepG2 cells.