Coactivator-associated arginine methyltransferase 1, CARM1, affects pre-mRNA splicing in an isoform-specific manner
Coactivator-associated arginine methyltransferase 1, CARM1, affects pre-mRNA splicing in an isoform-specific manner
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DOI：
10.1074/jbc.m502173200
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发表时间：
2005-08-12
影响因子：
4.8
通讯作者：
Tsukada, T
中科院分区：
文献类型：
--
作者：
Ohkura, N;Takahashi, M;Tsukada, T
通过选择性剪接的分子多样性对于细胞功能和发育是重要的。然而，很少有人知道的因素，调节选择性剪接。在这里，我们证明了一种亚型的辅激活相关精氨酸甲基转移酶1（命名为CARM 1-v3）与U1小核RNP特异性蛋白U1 C和影响5'剪接位点选择的前mRNA剪接。CARM 1-v3通过保留CARM 1初级转录物的内含子15和16而产生。其推导的蛋白质缺乏CARM 1主要同种型的C-末端结构域，而是在C末端具有v3特异性序列。当腺病毒E1 A小基因用作报道基因时，CARM 1-v3而不是其他同种型强烈刺激前体mRNA向远端5'剪接位点的转移，并增强CD 44报道基因中的外显子跳跃。缺乏v3特异性序列的CARM 1-v3突变体完全丧失了调节可变剪接模式的能力。此外，CARM 1-v3显示出与其他同种型不同的组织特异性表达模式。这些结果表明，转录辅激活因子可以影响剪接位点的决定，在异构体特异性的方式。
Molecular diversity through alternative splicing is important for cellular function and development. However, little is known about the factors that regulate alternative splicing. Here we demonstrate that one isoform of coactivator-associated arginine methyltransferase 1 (named CARM1-v3) associates with the U1 small nuclear RNP-specific protein U1C and affects 5' splice site selection of the pre-mRNA splicing. CARM1-v3 was generated by the retention of introns 15 and 16 of the primary transcript of CARM1. Its deduced protein lacks the C-terminal domain of the major isoform of CARM1 and instead has v3-specific sequences at the C terminus. CARM1-v3, but not the other isoforms, strongly stimulates a shift to the distal 5' splice site of the pre-mRNA when the adenoviral E1A minigene is used as a reporter and enhances the exon skips in the CD44 reporter. A CARM1-v3 mutant lacking the v3- specific sequences completely lost the ability to regulate the alternative splicing patterns. In addition, CARM1-v3 shows tissue-specific expression patterns distinct from those of the other isoforms. These results suggest that the transcriptional coactivator can affect the splice site decision in an isoform-specific manner.