• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Non-ATG-initiated translation directed by microsatellite expansions
【24h】

Non-ATG-initiated translation directed by microsatellite expansions

机译：由微卫星扩展定向的非ATG启动的翻译

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Trinucleotide expansions cause disease by both protein- and RNA-mediated mechanisms. Unexpectedly, we discovered that CAG expansion constructs express homopolymeric polyglutamine, pol-yalanine, and polyserine proteins in the absence of an ATG start codon. This repeat-associated non-ATG translation (RAN translation) occurs across long, hairpin-forming repeats in transfected cells or when expansion constructs are integrated into the genome in lentiviral-transduced cells and brains. Additionally, we show that RAN translation across human spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1) CAG expansion transcripts results in the accumulation of SCA8 polyalanine and DM1 polyglutamine expansion proteins in previously established SCA8 and DM1 mouse models and human tissue. These results have implications for understanding fundamental mechanisms of gene expression. Moreover, these toxic, unexpected, homopolymeric proteins now should be considered in pathogenic models of microsatellite disorders.
机译：三核苷酸的扩增通过蛋白质和RNA介导的机制引起疾病。出乎意料的是，我们发现CAG扩展构建体在没有ATG起始密码子的情况下表达均聚的聚谷氨酰胺，聚丙氨酸和聚丝氨酸蛋白。这种重复相关的非ATG翻译（RAN翻译）发生在转染细胞中长的，形成发夹结构的重复序列中，或者是在慢病毒转导的细胞和大脑中将扩展构建体整合到基因组中时发生的。此外，我们显示跨人小脑共济失调8型（SCA8）和强直性营养不良1型（DM1）CAG扩展转录本的RAN翻译导致SCA8聚丙氨酸和DM1聚谷氨酰胺扩展蛋白在先前建立的SCA8和DM1小鼠模型和人体组织中积累。这些结果对理解基因表达的基本机制具有影响。此外，现在应在微卫星疾病的致病模型中考虑这些有毒的，出乎意料的均聚物蛋白。

著录项

  • 来源
  • 作者

    Tao Zu; Brian Gibbens; Noelle S. Doty; Mario Gomes-Pereira; Aline Huguet; Matthew D. Stone; Jamie Margolis; Mark Peterson; Todd W. Markowski; Melissa A. C. Ingram; Zhenhong Nan; Colleen Forster; Walter C. Low; Benedikt Schoser; Nikunj V. Somia; H. Brent Clark; Stephen Schmechel; Peter B. Bitterman; Genevieve Gourdon; Maurice S. Swanson; Melinda Moseley; Laura P. W. Ranum;

  • 作者单位

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Translational Neuroscience,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Translational Neuroscience,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Translational Neuroscience,University of Minnesota Medical School, Minneapolis, MN 55455;

    lnstitut National de la Sante et de la Recherche Medicale U781, Universite Paris Descartes,Hopital Necker Enfants Malades, 75015 Paris, France;

    lnstitut National de la Sante et de la Recherche Medicale U781, Universite Paris Descartes,Hopital Necker Enfants Malades, 75015 Paris, France;

    Departments of Center for Mass Spectrometry and Proteomics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Biochemistry, Molecular Biology and Biophysics,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Translational Neuroscience,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Medicine,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Center for Mass Spectrometry and Proteomics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Biochemistry, Molecular Biology and Biophysics,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Translational Neuroscience,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Neurosurgery,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Laboratory Medicine and Pathology,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Neurosurgery,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Laboratory Medicine and Pathology,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Laboratory Medicine and Pathology,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Medicine,University of Minnesota Medical School, Minneapolis, MN 55455;

    lnstitut National de la Sante et de la Recherche Medicale U781, Universite Paris Descartes,Hopital Necker Enfants Malades, 75015 Paris, France;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Translational Neuroscience,University of Minnesota Medical School, Minneapolis, MN 55455;

    Departments of Genetics Cell Biology and Development,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Human Genetics,University of Minnesota Medical School, Minneapolis, MN 55455,Departments of Institute of Translational Neuroscience,University of Minnesota Medical School, Minneapolis, MN 55455;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    bidirectional expression; neurodegeneration; translation initiation;

    机译：双向表达;神经变性;翻译起始;
  • 入库时间 2022-08-18 00:40:42

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