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

Jung Chun Lin, Woan Yuh Tarn

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 splicingcoupled 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.

Original languageEnglish
Pages (from-to)509-520
Number of pages12
JournalJournal of Cell Biology
Volume193
Issue number3
DOIs
Publication statusPublished - May 2011
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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