Identification of the methylation preference region in heterogeneous nuclear ribonucleoprotein K by protein arginine methyltransferase 1 and its implication in regulating nuclear/cytoplasmic distribution
Identification of the methylation preference region in heterogeneous nuclear ribonucleoprotein K by protein arginine methyltransferase 1 and its implication in regulating nuclear/cytoplasmic distribution
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DOI：
10.1016/j.bbrc.2010.12.076
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发表时间：
2011-01-21
影响因子：
3.1
通讯作者：
Lin, Wey-Jinq
中科院分区：
文献类型：
--
作者：
Chang, Yuan-I;Hsu, Sheng-Chieh;Lin, Wey-Jinq
蛋白质精氨酸甲基化在许多细胞过程中起着至关重要的作用。异质核核糖核蛋白K（hnRNP K）是一种多功能蛋白质，参与多种细胞功能，包括转录和RNA加工。HnRNP K在甘氨酸和甘氨酸瑞克（RGG）基序中的多个位点处甲基化。利用hnRNP K的多种RGG结构域缺失突变体作为底物，在这里，我们通过直接甲基化测定显示蛋白质精氨酸甲基转移酶1（PRMT 1）在a.a. 280-307的RGG基序。动力学分析表明，a.a. 280-307，但不是戒酒会. 308-327，显著抑制甲基化率。重要的是，核定位的hnRNP K显着受损的突变体hnRNP K缺乏PRMT 1甲基化区域或甲基化的药理学抑制。总之，我们的研究结果确定了首选的PRMT 1甲基化序列的hnRNP K的直接甲基化试验，并暗示精氨酸甲基化的作用，在调节细胞内分布的hnRNP K。(C)2010年爱思唯尔公司All rights reserved.
Protein arginine methylation plays crucial roles in numerous cellular processes. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein participating in a variety of cellular functions including transcription and RNA processing. HnRNP K is methylated at multiple sites in the glycine- and arginine-rick(RGG) motif. Using various RGG domain deletion mutants of hnRNP K as substrates, here we show by direct methylation assay that protein arginine methyltransferase 1 (PRMT1) methylated preferentially in a.a. 280-307 of the RGG motif. Kinetic analysis revealed that deletion of a.a. 280-307, but not a.a. 308-327, significantly inhibited rate of methylation. Importantly, nuclear localization of hnRNP K was significantly impaired in mutant hnRNP K lacking the PRMT1 methylation region or upon pharmacological inhibition of methylation. Together our results identify preferred PRMT1 methylation sequences of hnRNP K by direct methylation assay and implicate a role of arginine methylation in regulating intracellular distribution of hnRNP K. (C) 2010 Elsevier Inc. All rights reserved.