Effect of SF3A1 inhibition on pre-mRNA splicing

We previously found that the SF3A mRNA splicing complex was required for a robust innate immune response; SF3A acts in part by inhibiting the production of a negatively acting splice form of the TLR signaling adaptor MyD88. Here we inhibit SF3A1 using RNAi and subsequently perform an RNAseq study to identify the full complement of genes and splicing events regulated by SF3A in murine macrophages. Surprisingly, SF3A has substantial specificity for mRNA splicing events in innate immune signaling pathways compared to other pathways, affecting the splicing of many genes in the TLR signaling pathway to modulate the innate immune response. Overall design: RNAseq was used to monitor the effects of SF3A1 siRNA-mediated knockdown in murine macrophages. Three biological replicates were used for each of the four treatment combinations (with/without siRNA, with/without LPS). The first replicates for each combination were each sequenced in two runs, which were combined in the analysis.

16

O'Connor BP, Danhorn T, De Arras L, Flatley BR, Marcus RA, Farias-Hesson E, Leach SM, Alper S