• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements
【24h】

The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements

机译：Mili的核酸内切酶活性促进piRNA扩增，使LINE1元件沉默

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

Piwi proteins and Piwi-interacting RNAs (piRNAs) have conserved functions in transposon silencing. The murine Piwi proteins Mili and Miwi (also called Piwi and Piwi, respectively) direct epi-genetic LINE1 and intracisternal A particle transposon silencing during genome reprogramming in the embryonic male germ line. Piwi proteins are proposed to be piRNA-guided endo-nudeases that initiate secondary piRNA biogenesis; however, the actual contribution of their endonuclease activities to piRNA biogenesis and transposon silencing remain unknown. To investigate the role of Piwi-catalysed endonucleolytic activity, we engineered point mutations in mice that substitute the second aspartic acid to an alanine in the DDH catalytic triad of Mili and Miwi2, generating the Mili~(DAH) and Miwi2~(DAH) alleles, respectively. Analysis of Mili-bound piRNAs from homozygous Mili~(DAH )fetal gonado-cytes revealed a failure of transposon piRNA amplification, resulting in the marked reduction of piRNA bound within Miwi2 ribonuclear particles. We find that Mili-mediated piRNA amplification is selectively required for LINE1, but not intracisternal A particle, silencing. The defective piRNA pathway in Mili~(DAH) mice results in spermatogenic failure and sterility. Surprisingly, homozygous Miwi2~(DAH) mice are fertile, transposon silencing is established normally and no defects in secondary piRNA biogenesis are observed. In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing.
机译：Piwi蛋白和Piwi相互作用RNA（piRNA）在转座子沉默中具有保守的功能。鼠Piwi蛋白Mili和Miwi（分别也称为Piwi和Piwi）在胚胎雄性生殖系中进行基因组重编程期间，指导表观遗传LINE1和脑池内A粒子转座子沉默。有人认为Piwi蛋白是piRNA指导的内切核酸酶，可引发继发piRNA生物发生。然而，其核酸内切酶活性对piRNA生物发生和转座子沉默的实际贡献仍然未知。为了研究Piwi催化的内切核酸酶活性的作用，我们设计了小鼠中的点突变，该突变在Mili和Miwi2的DDH催化三联体中将第二个天冬氨酸替换为丙氨酸，从而产生了Mili〜（DAH）和Miwi2〜（DAH）等位基因。 ， 分别。对纯合的Mili〜（DAH）胎儿性腺细胞的Mili结合的piRNA的分析显示，转座子piRNA扩增失败，导致Miwi2核糖核酸颗粒中结合的piRNA明显减少。我们发现，LINE1选择性需要Mili介导的piRNA扩增，而沉默脑池内A颗粒则不需要。 Mili〜（DAH）小鼠中有缺陷的piRNA途径导致生精失败和不育。出乎意料的是，纯合的Miwi2〜（DAH）小鼠可育，转座子沉默正常建立，未观察到继发piRNA生物发生的缺陷。此外，在Miwi2缺陷性腺细胞中观察到piRNA扩增的标志。我们得出的结论是，Mili内次生piRNA生物发生的周期促进了LINE1沉默绝对需要的piRNA扩增。

著录项

  • 来源
    《Nature》 |2011年第7376期|p.259-263|共5页
  • 作者

    Serena De Fazio; Nenad Bartonicek; Monica Di Giacomo; Cei Abreu-Goodger; Aditya Sankar; Charlotta Funaya; Claude Antony; Pedro N. Moreira; Anton J. Enright; Donal OCarroll;

  • 作者单位

    European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy;

    European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton,Cambridge CB10 1SD, UK;

    European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy;

    European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton,Cambridge CB10 1SD, UK;

    European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy;

    European Molecular Biology Laboratory, EMBL Meyerhof Str. 1,69117 Heidelberg, Germany;

    European Molecular Biology Laboratory, EMBL Meyerhof Str. 1,69117 Heidelberg, Germany;

    European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy;

    European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton,Cambridge CB10 1SD, UK;

    European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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

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