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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents



ID: 711839.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015
RBM24 is a major regulator of muscle-specific alternative splicing
Authors:Yang, J.; Hung, L. H.; Licht, T.; Kostin, S.; Looso, M.; Khrameeva, E.; Bindereif, A.; Schneider, A.; Braun, T.
Date of Publication (YYYY-MM-DD):2014-10-13
Title of Journal:Dev Cell
Volume:31
Issue / Number:1
Start Page:87
End Page:99
Audience:Not Specified
Abstract / Description: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.
Free Keywords:*Alternative Splicing; Animals; Exons; HeLa Cells; Heart/embryology; Heterogeneous-Nuclear Ribonucleoproteins/metabolism; Humans; Introns; Mice; Myocardium/metabolism; Organ Specificity; RNA-Binding Proteins/genetics/*metabolism; Sarcomeres/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:MPI für Herz- und Lungenforschung
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Institute of Biochemistry, University of Giessen, Heinrich-Buff-Ring 58, 35392 Giessen, Germany. Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoy Karetny per. 19, Moscow 127994, Russia. 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. 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. %^ 1435822261
Identifiers:ISSN:1878-1551 (Electronic) 1534-5807 (Linking) %R 10.1016/j.devcel.2014.08.025
URL:http://www.ncbi.nlm.nih.gov/pubmed/25313962
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