TY - JOUR
T1 - Exon selection in α-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB
AU - Lin, Jung Chun
AU - Tarn, Woan Yuh
PY - 2005/11
Y1 - 2005/11
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, 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=27644466946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27644466946&partnerID=8YFLogxK
U2 - 10.1128/MCB.25.22.10111-10121.2005
DO - 10.1128/MCB.25.22.10111-10121.2005
M3 - Article
C2 - 16260624
AN - SCOPUS:27644466946
SN - 0270-7306
VL - 25
SP - 10111
EP - 10121
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 22
ER -