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Molecular and Cellular Biology, November 2005, p. 10111-10121, Vol. 25, No. 22
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.22.10111-10121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Exon Selection in {alpha}-Tropomyosin mRNA Is Regulated by the Antagonistic Action of RBM4 and PTB

Jung-Chun Lin1,2 and Woan-Yuh Tarn1*

Institute of Biomedical Sciences, Academia Sinica,1 Institute of Molecular Medicine, College of Medicine, National Taiwan University Taipei, Taiwan2

Received 1 June 2005/ Returned for modification 5 July 2005/ Accepted 19 August 2005

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, {alpha}-tropomyosin ({alpha}-TM) is known to exhibit a muscle cell type-specific splicing pattern. The level of the skeletal muscle-specific {alpha}-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 {alpha}-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 {alpha}-TM by the antagonistic splicing regulators RBM4 and PTB.

* Corresponding author. Mailing address: Institute of Biomedical Sciences, Academia Sinica, 128 Academy Road Section 2, Nankang, Taipei 11529, Taiwan. Phone: 8862-26523052. Fax: 8862-27829142. E-mail: wtarn{at}ibms.sinica.edu.tw.

Molecular and Cellular Biology, November 2005, p. 10111-10121, Vol. 25, No. 22
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.22.10111-10121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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