...
  • 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 >Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation
【24h】

Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

机译：全基因组的RNA干扰筛查可识别以前未描述的聚谷氨酰胺聚集调节剂

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

Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation.
机译：蛋白质错误折叠和聚集体的形成是人类遗传疾病病理学中越来越多的公认组成部分，并且是许多神经退行性疾病的标志。如聚谷氨酰胺疾病所举例说明的，蛋白质错误折叠的倾向与聚谷氨酰胺扩展的长度和蛋白质折叠稳态中的年龄依赖性变化有关，这暗示了蛋白质稳态缓冲剂的关键作用。为了鉴定保护细胞免受蛋白质聚集体形成的蛋白质因子的补体，我们测试了在与年龄相关的蛋白质聚集现象相关的阈值长度下表达聚谷氨酰胺扩展黄色荧光蛋白融合蛋白的转基因秀丽隐杆线虫菌株。我们使用了全基因组的RNA干扰来鉴定被抑制后导致蛋白质聚集物过早出现的基因。我们的筛选确定了186种与聚谷氨酰胺调节剂的五种主要类别相对应的基因：涉及RNA代谢，蛋白质合成，蛋白质折叠和蛋白质降解的基因；以及那些参与蛋白质贩运的人。我们建议这些类别中的每一个代表一个分子机器，共同包括蛋白质稳态缓冲液，该缓冲液可响应受损蛋白质的表达以防止其错误折叠和聚集。

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