Rbfox1 – a hub controlling splicing and ncRNA fate in cardiovascular disease

The RBFOX-family of RNA-binding proteins (RBPs) constitutes a group of conserved regulators of alternative splicing (AS). RBFOX1 is mainly expressed in neurons and muscle tissue. This expression pattern is achieved by the use of alternative promoters and AS resulting in neuronal and muscular isoforms. Animal models confirmed the essential role of RBFOX1 in the regulation of alternative splicing. Hence, it was described that RBFOX1 is strongly decreased following transverse aortic constriction (TAC) in mice. In this model of cardiac hypertrophy several splicing changes have been observed, which could be partially explained by the loss of RBFOX1 expression. These studies suggested that a decrease in RBFOX1 expression correlates with pathologies that involve a progressive muscle de-differentiation (e.g. cardiac hypertrophy or muscle dystrophy). In addition to AS, RBFOX-variants had been implicated in the regulation of miRNA-biogenesis as well as influencing the processing of snoRNAs due to the association with a conserved GCAUG-motif in several precursor ncRNAs. So far, there is just limited information about the mechanisms underlying the de-regulation of RBFOX1-expression.