What we do and why

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One of the most exciting advances in the last decades is that of next-generation sequencing technologies, which has led to a much greater understanding of the extent of RNA splicing. In the 1980s, it was thought that about 5% of human genes were subjected to alternative splicing. Now, this number has risen to >95%, meaning that the vast majority of mRNAs are subjected to alternative splicing. Consequently, most protein-coding genes encode for multiple proteins with (slightly) different or even opposing functions. Studies on pivotal cardiac splicing factors have shown the importance and functional relevance of splicing in the heart. For example, mutations in the splicing factor RBM20 lead to an arrhythmogenic dilated cardiomyopathy, and a single SF3B1-coordinated switch in Ketohexokinase isoforms is sufficient to actuate cardiac fructose metabolism and drive cardiac dysfunction. These recent findings put RNA splicing on the map as an important additional regulator of cardiac function, and with our research, we aim to further unravel the splicing code in the heart.