Exon selection in α-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB
Exon selection in α-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB
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DOI：
10.1128/mcb.25.22.10111-10121.2005
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发表时间：
2005-11-01
影响因子：
5.3
通讯作者：
Tarn, WY
中科院分区：
文献类型：
--
作者：
Lin, JC;Tarn, WY
RNA结合基序蛋白4（RBM 4）参与前体mRNA剪接的调节。使用差异显示分析，我们确定了与RBM 4含有信使RNP在体内的mRNA。在这些mRNA中，已知α-原肌球蛋白（α-TM）表现出肌细胞类型特异性剪接模式。骨骼肌特异性α-TM mRNA亚型的水平部分相关的RBM 4在人体组织检查，并可以通过异位过表达或抑制RBM 4调制。这些结果表明RBM 4直接影响骨骼肌特异性α-TM亚型的表达。使用小基因，我们证明了RBM 4可以激活骨骼肌特异性外显子的选择，可能是通过结合内含子嘧啶丰富的元素。相比之下，剪接调节剂聚嘧啶道结合蛋白（PTB）排除这些外显子，而且，RBM 4拮抗这种PTB介导的外显子排斥可能通过与PTB竞争结合到一个CU丰富的元素。这项研究表明，一个可能的机制的调节alpha-TM的选择性剪接的拮抗剪接调节RBM 4和PTB。
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.