• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Biochemical determinants for the assembly of RNA induced silencing complexes in Drosophila melanogaster.
【24h】

Biochemical determinants for the assembly of RNA induced silencing complexes in Drosophila melanogaster.

机译：果蝇决定果蝇中RNA诱导沉默复合物组装的生化决定因素。

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

In order to understand how a gene issues instructions to bring about life, we need to understand when, where, and to what extent it is functioning. The recent discovery of conserved small RNA-based silencing pathways has fostered a new appreciation for the startling complexity underlying the coordinated regulation of gene expression. In Drosophila, the RNA interference (RNAi) pathway and other small RNA-related gene silencing mechanisms assemble complex macromolecular machines to bring about mRNA degradation, heterochromatin rearrangement, translational repression, and possibly other forms of sequence-specific regulation. Here I focus on several key steps in the assembly process of the mRNA-degrading holo-enzyme of RNAi (called RISC) and also report the discovery of a new silencing factor that may be a core component of a previous unknown small RNA-related gene regulation machine that is essential for male gametogenesis.;Drosophila RNAi is initiation by the processing of long double-stranded RNA (dsRNA) into short, 21 nucleotide small interfering RNA (siRNA) duplexes by the double-stranded RNA endonuclease Dicer. I investigated the relationship between Dicer processing and selection of the siRNA guide strand that is loaded into the active site of RISC. I found that the generation of an siRNA from a long double-stranded precursor and the initiation of RISC assembly are two biochemically distinct events, despite a mutual requirement for the enzyme Dicer-2. Subsequently, I observed that ubiquitin-mediated signals influence the RNAi pathway. Specifically, RISC maturation is dependent upon a ubiquitin conjugation event that is independent of the ubiquitin-proteasome pathway. This observation is consistent with recent findings that RNAi components associate with endosomes and the multivesicular body, each of which utilize ubiquitin-mediated signals to sort cargo between intracellular membranes.;I also worked to characterize a novel pair of double-stranded RNA binding proteins that are critical for Drosophila spermatogenesis. These proteins contribute to RNA silencing in cell culture, and loss of expression in the germline leads to spermatogenic defects and sterility. A novel mRNA-derived small RNA population is dependent upon at least one of these proteins for their sustainability, and their sequences suggest they may play a direct role in regulating genes that are essential for spermiogenesis.
机译：为了了解基因是如何发出指令以实现生命的，我们需要了解其何时，何地以及在何种程度上起作用。保守的基于小RNA的沉默途径的最新发现促进了对基因表达协调调控背后的惊人复杂性的新认识。在果蝇中，RNA干扰（RNAi）途径和其他与RNA相关的小基因沉默机制组装了复杂的大分子机器，以引起mRNA降解，异染色质重排，翻译抑制以及可能的其他形式的序列特异性调控。在这里，我重点介绍RNAi的mRNA降解全酶（称为RISC）组装过程中的几个关键步骤，并报告了新的沉默因子的发现，该沉默因子可能是以前未知的小RNA相关基因的核心成分。果蝇RNAi是通过双链RNA内切酶切酶酶将长双链RNA（dsRNA）加工成短的21个核苷酸的小干扰RNA（siRNA）双链体而引发的。我研究了Dicer加工与选择RISRNA活性位点的siRNA引导链的选择之间的关系。我发现从长双链前体生成siRNA和RISC组装的启动是两个生化上不同的事件，尽管对Dicer-2酶有共同的需求。随后，我观察到泛素介导的信号影响RNAi途径。具体地说，RISC的成熟取决于与泛素-蛋白酶体途径无关的泛素结合事件。这一观察结果与最近的发现一致，即RNAi成分与内体和多囊泡体相关，它们均利用泛素介导的信号在细胞内膜之间分拣货物。;我还致力于表征一对新的双链RNA结合蛋白，该蛋白对果蝇的精子发生至关重要。这些蛋白质有助于细胞培养中的RNA沉默，种系中表达的丧失会导致生精缺陷和不育。一种新的源自mRNA的小RNA群体的可持续性依赖于这些蛋白质中的至少一种，其序列表明它们可能在调节精子发生必不可少的基因中发挥直接作用。

著录项

  • 作者

    Preall, Jonathan B.;

  • 作者单位

    Northwestern University.;

  • 授予单位 Northwestern University.;
  • 学科 Biology Molecular.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 218 p.
  • 总页数 218
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:38:26

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