...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements
【24h】

Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements

机译:动态组蛋白乙酰化对于共转录剪接体组装和剪接体重排至关重要

获取原文
获取原文并翻译 | 示例
           

摘要

Assembly of the spliceosome onto pre-mRNA is a dynamic process involving the ordered exchange of snRNPs to form the catalytically active spliceosome. These ordered rearrangements have recently been shown to occur cotranscriptionally, while the RNA polymerase is still actively engaged with the chromatin template. We previously demonstrated that the histone acetyltransferase Gcn5 is required for U2 snRNP association with the branchpoint. Here we provide evidence that histone acetylation and deacetylation facilitate proper cotranscriptional association of spliceosomal snRNPs. As with GCN5, mutation or deletion of Gcn5-targeted histone H3 residues leads to synthetic lethality when combined with deletion of the genes encoding the U2 snRNP components Leal or Msl1. Gcn5 associates throughout intron-containing genes and, in the absence of the histone deacetylases Hos3 and Hos2, enhanced histone H3 acetylation is observed throughout the body of genes. Deletion of histone deacetylaces also results in persistent association of the U2 snRNP and a severe defect in the association of downstream factors. These studies show that cotranscriptional spliceosome rearrangements are driven by dynamic changes in the acetylation state of histones and provide a model whereby yeast spliceosome assembly is tightly coupled to histone modification.
机译:剪接体组装到前mRNA上是一个动态过程,涉及snRNPs的有序交换以形成催化活性剪接体。这些有序的重排最近已显示出共转录发生,而RNA聚合酶仍活跃地与染色质模板结合。我们先前证明,组蛋白乙酰转移酶Gcn5是U2 snRNP与分支点结合所必需的。在这里,我们提供了组蛋白乙酰化和脱乙酰化促进剪接体snRNPs正确共转录结合的证据。与GCN5一样,当与编码U2 snRNP成分Leal或Msl1的基因删除结合时,靶向Gcn5的组蛋白H3残基的突变或缺失会导致合成杀伤力。 Gcn5关联整个含内含子的基因,并且在没有组蛋白脱乙酰基酶Hos3和Hos2的情况下,在整个基因体内都观察到增强的组蛋白H3乙酰化。组蛋白脱乙酰基的缺失也导致U2 snRNP的持续结合和下游因子结合的严重缺陷。这些研究表明,共转录剪接体重排是由组蛋白的乙酰化状态的动态变化驱动的,并提供了一种模型,其中酵母剪接体组装紧密地与组蛋白修饰偶联。

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