title: Emerging Role for RBM20 and its Splicing Substrates in Cardiac Function and Heart Failure.
abstract: Heart failure is one of the devastating public health problems with high mortality. Among various contributing factors for heart failure, severe dilated cardiomyopathy is the most common indication for cardiac transplantation. Recent evidence revealed that RBM20 mutation represents one main cause for familial dilated cardiomyopathy with a 3% prevalence in all forms of dilated cardiomyopathy. Further scrutiny of molecular mechanisms suggests a role for RBM20 as a functional splicing factor for protein isoform transition, indicating the clinical value of RBM20 mutations in the diagnosis and treatment of heart diseases. RBM20 alternatively splices a set of genes including titin, CaMKIID, and GIT2 at the post transcriptional level to yield diverse isoforms. These target proteins are necessary for cardiac homeostasis including structure and signal transduction. Mutations in RBM20 cause dilated cardiomyopathy along with dysregulated isoform switch. This review aims to summarize the current knowledge of RBM20-related dilated cardiomyopathy and heart failure as well as the underlying mechanism. We will emphasize and thoroughly discuss two splicing targets including titin and CaMKII which are known to play a vital role in dilated cardiomyopathy and heart failure.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Ma
authors.forename: Linhe
authors.initials: L
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: College of Health Sciences, University of Wyoming, Laramie, Wyoming, 82071, USA. jren@uwyo.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi&#39;an, 710032, China. yangjian1212@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D016601:RNA-Binding Proteins; C543725:ribonucleic acid binding motif protein 20, human