• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Prolyl 4-hydroxylation regulates Argonaute 2 stability
【24h】

Prolyl 4-hydroxylation regulates Argonaute 2 stability

机译：脯氨酰4-羟基化调节Argonaute 2的稳定性

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

Human Argonaute (Ago) proteins are essential components of the RNA-induced silencing complexes (RISCs). Argonaute 2 (Ago2) has a P-element-induced wimpy testis (PIWI) domain, which folds like RNase H and is responsible for target RNA cleavage in RNA interference. Proteins such as Dicer, TRBP, MOV10, RHA, RCK/p54 and KIAA1093 associate with Ago proteins and participate in small RNA processing, RISC loading and localization of Ago proteins in the cytoplasmic messenger RNA processing bodies1'2. However, mechanisms that regulate RNA interference remain obscure. Here we report physical interactions between Ago2 and the α-(P4H-α(I)) and β(P4H-β) subunits of the type I collagen prolyl-4-hydroxylase (C-P4H(I)). Mass spectrometric analysis identified hydroxylation of the endogenous Ago2 at proline 700. In vitro, both Ago2 and Ago4 seem to be more efficiently hydroxylated than Agol and Ago3 by recombinant human C-P4H(I). Importantly, human cells depleted of P4H-α(I) or P4H-β by short hairpin RNA and P4H-α(I) null mouse embryonic fibroblast cells showed reduced stability of Ago2 and impaired short interfering RNA programmed RISC activity. Furthermore, mutation of proline 700 to alanine also resulted in destabilization of Ago2, thus linking Ago2 P700 and hydroxylation at this residue to its stability regulation. These findings identify hydroxylation as a post-translational modification important for Ago2 stability and effective RNA interference.
机译：人类Argonaute（Ago）蛋白是RNA诱导的沉默复合物（RISC）的重要组成部分。 Argonaute 2（Ago2）具有一个P元素诱导的w弱的睾丸（PIWI）域，该区域像RNase H一样折叠，并负责RNA干扰中的靶RNA裂解。诸如Dicer，TRBP，MOV10，RHA，RCK / p54和KIAA1093之类的蛋白质与Ago蛋白质缔合，并参与小RNA加工，RISC加载和Ago蛋白质在细胞质信使RNA加工体中的定位1'2。但是，调节RNA干扰的机制仍然不清楚。在这里，我们报告Ago2与I型胶原脯氨酰-4-羟化酶（C-P4H（I））的α-（P4H-α（I））和β（P4H-β）亚基之间的物理相互作用。质谱分析鉴定了脯氨酸700处内源性Ago2的羟基化。在体外，重组人C-P4H（I）似乎比Agol和Ago3都更有效地羟基化了Ago2和Ago4。重要的是，通过短发夹RNA和P4H-α（I）缺失的小鼠胚胎成纤维细胞耗尽了P4H-α（I）或P4H-β的人类细胞显示出Ago2的稳定性降低，短时RNA干扰的RISC活性受损。此外，脯氨酸700突变为丙氨酸还导致Ago2不稳定，因此将Ago2 P700和该残基处的羟基化与其稳定性调节联系起来。这些发现确定羟基化是对Ago2稳定性和有效RNA干扰重要的翻译后修饰。

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