The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing
The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing
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DOI：
10.1016/j.molcel.2006.11.019
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发表时间：
2007-01-12
期刊：
影响因子：
16
通讯作者：
Bedford, Mark T.
中科院分区：
文献类型：
--
作者：
Cheng, Donghang;Cote, Jocelyn;Bedford, Mark T.
共激活剂相关的精氨酸甲基转移酶 CARM1 被许多不同的转录因子招募作为正调节因子。为了了解 CARM1 的作用机制，我们试图分离其底物。为此，我们开发了一种小池筛选方法，并将 CA150、SAP49、SmB 和 U1C 确定为被 CARM1 特异性甲基化的剪接因子。我们进一步表明，CA150（一种将转录与剪接联系起来的分子）以 CARM1 依赖性方式与脊髓性肌萎缩蛋白 SMN 的 Tudor 结构域相互作用。使用外源剪接报告基因和内源 CD44 基因进行的实验表明，CARM1 以酶依赖性方式促进外显子跳跃。由 CARM1 甲基化的剪接因子以及由 CARIVIII 调节的蛋白质-蛋白质相互作用的鉴定，强烈暗示该酶参与可变剪接的调节，并指出其参与脊髓性肌萎缩症的发病机制。
The coactivator-associated arginine methyltransferase CARM1 is recruited by many different transcription factors as a positive regulator. To understand the mechanism by which CARM1 functions, we sought to isolate its substrates. We developed a small-pool screening approach for this purpose and identified CA150, SAP49, SmB, and U1C as splicing factors that are specifically methylated by CARM1. We further showed that CA150, a molecule that links transcription to splicing, interacts with the Tudor domain of the spinal muscular atrophy protein SMN in a CARM1 -dependent fashion. Experiments with an exogenous splicing reporter and the endogenous CD44 gene revealed that CARM1 promotes exon skipping in an enzymedependent manner. The identification of splicing factors that are methylated by CARM1, and protein-protein interactions that are regulated by CARIVIII, strongly implicates this enzyme in the regulation of alternative splicing and points toward its involvement in spinal muscular atrophy pathogenesis.