A novel WD repeat protein component of the methylosome binds Sm proteins

A novel WD repeat protein component of the methylosome binds Sm proteins
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DOI:
10.1074/jbc.m109984200
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发表时间:
2002-03-08
影响因子:
4.8
通讯作者:
Dreyfuss, G
Dreyfuss, G
中科院分区:
生物学2区
文献类型:
--
作者:
Friesen, WJ;Wyce, A;Dreyfuss, G

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我们最近描述了一个大的(20 S)蛋白精氨酸甲基转移酶复合物,称为甲基体,其中包含甲基转移酶JBP1(PRMT5)和pICln蛋白。甲基化体的功能,以修改特定的精氨酸,二甲基精氨酸在精氨酸和甘氨酸丰富的几个剪接体Sm蛋白的结构域,这种修改的目标是这些蛋白质的生存运动神经元(SMN)复杂的组装成小核核糖核蛋白(snRNP)的核心颗粒。在这里,我们描述了一个新的组成部分的甲基体,一个50千道尔顿的WD重复蛋白称为甲基体蛋白50(MEP 50)。我们发现,MEP 50是重要的甲基体活性,并结合到JBP 1和Sm蛋白的一个子集。由于WD重复蛋白为多种蛋白相互作用提供了一个平台,因此MEP 50可能起到介导多种底物与甲基化体相互作用的作用。有趣的是,所有已知的组件的甲基体结合Sm蛋白,这表明除了生产适当的甲基化的SMN复合物的底物,甲基体可能参与Sm蛋白重排或预组装所需的snRNP生物合成。
We have recently described a large (20 S) protein arginine methyltransferase complex, termed the methylosome, that contains the methyltransferase JBP1 (PRMT5) and the pICln protein. The methylosome functions to modify specific arginines to dimethylarginines in the arginine- and glycine-rich domains of several spliceosomal Sm proteins, and this modification targets these proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein (snRNP) core particles. Here, we describe a novel component of the methylosome, a 50-kilodalton WD repeat protein termed methylosome protein 50 (MEP50). We show that MEP50 is important for methylosome activity and binds to JBP1 and to a subset of Sm proteins. Because WD repeat proteins provide a platform for multiple protein interactions, MEP50 may function to mediate the interaction of multiple substrates with the methylosome. Interestingly, all of the known components of the methylosome bind Sm proteins, suggesting that in addition to producing properly methylated substrates for the SMN complex, the methylosome may be involved in Sm protein rearrangements or pre-assembly required for snRNP biogenesis.