Analysis of alternative exon-dependent interactome remodelling reveals multitasking functions of gene regulatory factors (Sap30bp RNA-Seq). Analysis of alternative exon-dependent interactome remodelling reveals multitasking functions of gene regulatory factors (Sap30bp RNA-Seq)

Alternative splicing is fundamental for the expansion of biological complexity, particularly in the vertebrate nervous system. Increasing evidence indicates that developmental stage and tissue-dependent alternative exons often control protein-protein interactions, yet only a minor fraction of these events has been characterized at the protein level. Using affinity purification-mass spectrometry (AP-MS) we show that approximately 60% of analyzed neural-differential exons in proteins previously implicated in transcriptional regulation result in the gain or loss of interaction partners. Focusing on Chtop and Sap30bp, the neural exons in these proteins unexpectedly remodel interactions with partners associated with mRNA processing and trafficking. Sap30bp additionally controls RNA localization by regulating the splicing of <100 nt ‘mini-introns’ that contribute to the nuclear retention of transcripts. These activities of Chtop and Sap30bp are linked to programs of transcriptomic regulation associated with development of the nervous system. AP-MS is thus a powerful approach for elucidating multifaceted functions of proteins imparted by context-dependent alternative exons. Overall design: This dataset consists of 12 RNA-seq files associated with the manuscript "Analysis of alternative exon-dependent interactome remodelling reveals multitasking functions of gene regulatory factors" characterizing the effect of Sap30bp siRNA knockdown and neural/non-neural isoform rescue on gene expression and splicing in Neuro2a cell lines. For each isoform (with or without exon 3), a total of 6 samples were analyzed including non-targeting control (NTC), Sap30bp siRNA knockdown, and siRNA knockdown with Doxycycline-induced rescue with an siRNA-resistant Sap30bp cDNA performed in two biological replicates.