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Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB.
Mol Cell Biol. 2005 Nov; 25(22):10111-21.MC

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, 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.

Authors+Show Affiliations

Institute of Biomedical Sciences, Academia Sinica, 128 Academy Road Section 2, Nankang, Taipei 11529, Taiwan.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16260624

Citation

Lin, Jung-Chun, and Woan-Yuh Tarn. "Exon Selection in Alpha-tropomyosin mRNA Is Regulated By the Antagonistic Action of RBM4 and PTB." Molecular and Cellular Biology, vol. 25, no. 22, 2005, pp. 10111-21.
Lin JC, Tarn WY. Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB. Mol Cell Biol. 2005;25(22):10111-21.
Lin, J. C., & Tarn, W. Y. (2005). Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB. Molecular and Cellular Biology, 25(22), 10111-21.
Lin JC, Tarn WY. Exon Selection in Alpha-tropomyosin mRNA Is Regulated By the Antagonistic Action of RBM4 and PTB. Mol Cell Biol. 2005;25(22):10111-21. PubMed PMID: 16260624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB. AU - Lin,Jung-Chun, AU - Tarn,Woan-Yuh, PY - 2005/11/2/pubmed PY - 2005/12/17/medline PY - 2005/11/2/entrez SP - 10111 EP - 21 JF - Molecular and cellular biology JO - Mol. Cell. Biol. VL - 25 IS - 22 N2 - 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. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/16260624/Exon_selection_in_alpha_tropomyosin_mRNA_is_regulated_by_the_antagonistic_action_of_RBM4_and_PTB_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=16260624 DB - PRIME DP - Unbound Medicine ER -