Format

Send to

Choose Destination
See comment in PubMed Commons below
Dev Cell. 2014 Oct 13;31(1):87-99. doi: 10.1016/j.devcel.2014.08.025.

RBM24 is a major regulator of muscle-specific alternative splicing.

Author information

1
Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
2
Institute of Biochemistry, University of Giessen, Heinrich-Buff-Ring 58, 35392 Giessen, Germany.
3
Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoy Karetny per. 19, Moscow 127994, Russia.
4
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.
5
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.

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.

PMID:
25313962
DOI:
10.1016/j.devcel.2014.08.025
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center