• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Arginine Methylation Controls the Subcellular Localization and Functions of the Oncoprotein Splicing Factor SF2/ASF
【24h】

Arginine Methylation Controls the Subcellular Localization and Functions of the Oncoprotein Splicing Factor SF2/ASF

机译：精氨酸甲基化控制癌蛋白剪接因子SF2 / ASF的亚细胞定位和功能。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Alternative splicing and posttranslational modifications (PTMs) are major sources of protein diversity in eukaryotic proteomes. The SR protein SF2/ASF is an oncoprotein that functions in pre-mRNA splicing, with additional roles in other posttranscriptional and translational events. Functional studies of SR protein PTMs have focused exclusively on the reversible phosphorylation of Ser residues in the C-terminal RS domain. We confirmed that human SF2/ASF is methylated at residues R93, R97, and R109, which were identified in a global proteomic analysis of Arg methylation, and further investigated whether these methylated residues regulate the properties of SF2/ASF. We show that the three arginines additively control the subcellular localization of SF2/ASF and that both the positive charge and the methylation state are important. Mutations that block methylation and remove the positive charge result in the cytoplasmic accumulation of SF2/ASF. The consequent decrease in nuclear SF2/ASF levels prevents it from modulating the alternative splicing of target genes, results in higher translation stimulation, and abrogates the enhancement of nonsense-mediated mRNA decay. This study addresses the mechanisms by which Arg methylation and the associated positive charge regulate the activities of SF2/ASF and emphasizes the significance of localization control for an oncoprotein with multiple functions in different cellular compartments.
机译：选择性剪接和翻译后修饰（PTM）是真核蛋白质组中蛋白质多样性的主要来源。 SR蛋白SF2 / ASF是一种癌蛋白，可在mRNA剪接之前发挥功能，并在其他转录后和翻译事件中发挥额外作用。 SR蛋白PTM的功能研究仅集中于C端RS结构域中Ser残基的可逆磷酸化。我们确认人类SF2 / ASF在残基R93，R97和R109处被甲基化，这些残基已在Arg甲基化的全球蛋白质组学分析中确定，并进一步研究了这些甲基化的残基是否调节SF2 / ASF的特性。我们表明，三个精氨酸可加性控制SF2 / ASF的亚细胞定位，并且正电荷和甲基化状态都很重要。阻断甲基化并去除正电荷的突变导致SF2 / ASF的细胞质积累。随之而来的核SF2 / ASF含量降低，阻止了它调节靶基因的可变剪接，导致更高的翻译刺激，并废除了无义介导的mRNA衰变的增强。这项研究探讨了Arg甲基化和相关的正电荷调节SF2 / ASF活性的机制，并强调了在多种细胞隔室中具有多种功能的癌蛋白的定位控制的重要性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号