Exon selection in α-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB

Jung Chun Lin, Woan Yuh Tarn

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

RNA-binding motif protein 4 (RBM4) has been implicated in the regulation of precursor mRNA splicing. Using differential display analysis, we identified mRNAs that associate with RBM4-containing messenger RNPs in vivo. Among these mRNAs, α-tropomyosin (α-TM) is known to exhibit a muscle cell type-specific splicing pattern. The level of the skeletal muscle-specific α-TM mRNA isoform partially correlated with that of RBM4 in human tissues examined and could be modulated by ectopic overexpression or suppression of RBM4. These results indicated that RBM4 directly influences the expression of the skeletal muscle-specific α-TM isoform. Using minigenes, we demonstrated that RBM4 can activate the selection of skeletal muscle-specific exons, possibly via binding to intronic pyrimidine-rich elements. By contrast, the splicing regulator polypyrimidine tract binding protein (PTB) excluded these exons; moreover, RBM4 antagonized this PTB-mediated exon exclusion likely by competing with PTB for binding to a CU-rich element. This study suggests a possible mechanism underlying the regulated alternative splicing of α-TM by the antagonistic splicing regulators RBM4 and PTB.

Original languageEnglish
Pages (from-to)10111-10121
Number of pages11
JournalMolecular and Cellular Biology
Volume25
Issue number22
DOIs
Publication statusPublished - Nov 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Exon selection in α-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB'. Together they form a unique fingerprint.

  • Cite this