Abstract 24043: Cytosolic RBFox1 in Cardiac Fibrosis Regulation

RBFox1 is known to be an RNA splicing regulator with enriched expression in cardiac muscle. Loss of RBFox1 expression is a molecular hallmark associated with pathological hypertrophy and heart failure. However, much of our current knowledge about RBFox1 focuses on nuclear RBFox1 with a major impact on global alternative splicing changes in the diseased heart. Yet, RBFox1 gene also generates a cytosolic isoform through alternative splicing (RBFox1c), but the specific function of RBFox1c in heart has not been characterized. RBFox1c expression is significantly repressed in the mouse failing heart and hypertrophic cardiomyocytes. We performed RNA-seq combined with GO and IPA analysis to determine the impact of RBFox1c expression in culture. Among the genes suppressed specifically by RBFox1c but not the nucleus RBFox1 are groups of pro-inflammatory genes. Both Motif enrichment analysis and de novo motif discovery identified significant enrichment of RBFox1 binding motif in the 3’UTRs of the RBFox1c regulated g...