Abstract 306: A Novel PKCalpha Splicing Isoform in Signaling for Cardiac Hypertrophy

RNA splicing is a significant post-transcriptional regulatory step to enrich the overall transcriptome complexity, yet its specific contribution to cardiac development and pathogenesis remains underexplored. Here, we performed a comprehensive deep RNA-seq analysis in murine heart to investigate the cardiac transcriptome at single exon-resolution. From the dataset, we have identified a previously un-annotated novel exon in the PKCα transcript ---PKCα-NE (Novel Exon). The novel exon encode a 16 amino acid insert adjacent to the PKCα turn motif. Interestingly, the splicing event is detected only in cardiac and skeletal muscle. Based on bioinformatics analysis, we have identified two highly conserved binding motifs for a cardiac splicing regulator_RBFox1. We further demonstrated that RBFox1 indeed functions as a positive regulator for the splicing event of this novel exon. In vitro studies showed that the NE converts PKCα from a lipid-dependent enzyme to a constitutively active kinase with high levels of auto...