title: RBM24 is a major regulator of muscle-specific alternative splicing.
abstract: Cell-type-specific splicing generates numerous alternatively spliced transcripts playing important roles for organ development and homeostasis, but only a few tissue-specific splicing factors have been identified. We found that RBM24 governs a large number of muscle-specific splicing events that are critically involved in cardiac and skeletal muscle development and disease. Targeted inactivation of RBM24 in mice disrupted cardiac development and impaired sarcomerogenesis in striated muscles. In vitro splicing assays revealed that recombinant RBM24 is sufficient to promote muscle-specific exon inclusion in nuclear extracts of nonmuscle cells. Furthermore, we demonstrate that binding of RBM24 to an intronic splicing enhancer (ISE) is essential and sufficient to overcome repression of exon inclusion by an exonic splicing silencer (ESS) containing PTB and hnRNP A1/A2 binding sites. Introduction of ESS and ISE converted a constitutive exon into an RMB24-dependent alternative exon. We reason that RBM24 is a major regulator of alternative splicing in striated muscles.
authors.affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry, University of Giessen, Heinrich-Buff-Ring 58, 35392 Giessen, Germany.
authors.forename: Lee-Hsueh
authors.initials: LH
authors.lastname: Hung
authors.affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Licht
authors.affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Looso
authors.affiliation: Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoy Karetny per. 19, Moscow 127994, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Khrameeva
authors.affiliation: Institute of Biochemistry, University of Giessen, Heinrich-Buff-Ring 58, 35392 Giessen, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bindereif
authors.affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany. Electronic address: andre.schneider@mpi-bn.mpg.de.
authors.forename: Andre
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany. Electronic address: thomas.braun@mpi-bn.mpg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D005091:Exons; D006367:HeLa Cells; D006321:Heart / Q000196:embryology; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D007438:Introns; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012518:Sarcomeres / Q000378:metabolism*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D016601:RNA-Binding Proteins; C547648:Rbm24 protein, mouse