RBM24 Is a major regulator of muscle-specific alternative splicing

Jiwen Yang, Lee Hsueh Hung, Thomas Licht, Sawa Kostin, Mario Looso, Ekaterina Khrameeva, Albrecht Bindereif, Andre Schneider, Thomas Braun

Research output: Contribution to journalArticlepeer-review

94 Citations (SciVal)

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. Invitro 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.

Original languageEnglish
Pages (from-to)87-99
Number of pages13
JournalDevelopmental Cell
Volume31
Issue number1
DOIs
Publication statusPublished - 13 Oct 2014
Externally publishedYes

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