Figure 3: TAF15 and FUS exhibit similar RNA interaction profiles in the mouse brain.

(a) Fold change in binding enrichment of TAF15, FUS, TDP-43, NOVA1 and RBFOX1 after normalization to the average length of proximal introns (dark blue), distal introns (light blue), exons (green), 5′ UTRs (purple) or 3′ UTRs (red). (b) An example of 3′ UTR binding by TAF15 (red) and FUS (green) but not by TDP-43 (purple) to Neurobeachin (Nbea) mRNA (chr3:55,428,730-55,433,169) in the mouse brain. RNA-seq results showing expression of Nbea is shown in blue. (c) Bar graph showing the per cent of gene targets that are common (black bars) or unique (white bars) to TAF15 and FUS, TDP-43 or both FUS and TDP-43. (d) An example of intronic ‘saw-tooth’ binding by TAF15 (red) and FUS (green) but not by TDP-43 (purple) to the glutamate receptor delta-1 subunit precursor (Grid1) mRNA (chr14:35,634,350-36,071,292) in the mouse brain. RNA-seq results showing expression of Grid1 is shown in blue. (e) Confirmation of reduced TAF15 expression in the mouse striatum by western blot analysis (left) and qPCR (right). Knockdown was achieved by intrastrial injection of ASOs complementary to TAF15 or a control ASO. Error bars represent s.d. (f,g) Venn diagrams showing overlap of genes downregulated (f) and upregulated (g) upon loss of TAF15, FUS or TDP-43 in the mouse striatum. (h–j) Per cent of genes that are downregulated (h), upregulated (i) or unchanged (j) upon ASO-mediated knockdown of the indicated RBP that has at least one binding site (target, grey) or no binding sites (non-target, black) by that RBP. Asterisks denote significant difference between target and non-target genes by Fisher’s exact test at P<0.05.