RBM20 role in FHOD3 alternative splicing regulation

RNA Binding Motif 20 is an RNA-binding protein acting as a regulator of mRNA splicing of a subset of expressed genes that play a key role in cardiac function. Mutations in the RBM2 gene are linked to familial dilated cardiomyopathy. The aim of this study is to analyze the functional role ofRBM20 protein in splicing regulation. we selected the “Formin Homology 2 Domain containing protein 3” (FHOD3) gene as a molecular target for RBM20 splicing regulation. Weapplied bioinformatics analysis in order to identify the putative cis -regulatory splicing signalsrequired for FHOD3 alternative transcripts expression. The results located potential consensus sequences for binding of RNA binding proteins in the exon-intron boundaries of 11-12-13 exons of the FHOD3 transcripts. Based on this information we are developing a FHOD3minigene that will be tested in transfected cells for functional analysis of RBM20. We expect that this molecular tool will help to elucidate the mechanism of alternative splicing mediated by tissue-specific ribonucleoproteins and will contribute to clarify the molecular pathogenesis of familiar dilated cardiomyopathy