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J Cell Biol. 2011 May 2;193(3):509-20. doi: 10.1083/jcb.201007131. Epub 2011 Apr 25.

RBM4 down-regulates PTB and antagonizes its activity in muscle cell-specific alternative splicing.

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  • 1Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan.


Alternative splicing contributes largely to cell differentiation and functional specification. We previously reported that the RNA-binding protein RBM4 antagonizes the activity of splicing factor PTB to modulate muscle cell-specific exon selection of α-tropomyosin. Here we show that down-regulation of PTB and its neuronal analogue nPTB during muscle cell differentiation may involve alternative splicing-coupled nonsense-mediated mRNA decay. RBM4 regulates PTB/nPTB expression by activating exon skipping of their transcripts during myogenesis. Moreover, RBM4 and PTB target a common set of transcripts that undergo muscle cell-specific alternative splicing. Overexpression of RBM4 invariably promoted expression of muscle cell-specific isoforms, which recapitulated in vivo alternative splicing changes during muscle differentiation, whereas PTB acted oppositely to RBM4 in expression of mRNA isoforms specific for late-stage differentiation. Therefore, RBM4 may synergize its effect on muscle cell-specific alternative splicing by down-regulating PTB expression and antagonizing the activity of PTB in exon selection, which highlights a hierarchical role for RBM4 in a splicing cascade that regulates myogenesis.

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