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血管生成素诱导的 tRNA 衍生应激诱导 RNA 促进应激诱导的应激颗粒组装。

Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly.

机构信息

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston,Massachusetts 02115, USA.

出版信息

J Biol Chem. 2010 Apr 2;285(14):10959-68. doi: 10.1074/jbc.M109.077560. Epub 2010 Feb 3.

Abstract

Angiogenin (ANG) is a secreted ribonuclease that cleaves tRNA to initiate a stress-response program in mammalian cells. Here we show that ANG inhibits protein synthesis and promotes arsenite- and pateamine A-induced assembly of stress granules (SGs). These effects are abrogated in cells transfected with the ANG inhibitor RNH1. Transfection of natural or synthetic 5'- but not 3'-tRNA fragments (tRNA-derived stress-induced RNAs; tiRNAs) induces the phospho-eukaryotic translation initiation factor 2alpha-independent assembly of SGs. Natural 5'-tiRNAs but not 3'-tiRNAs are capped with a 5'-monophosphate that is required for optimal SG assembly. These findings reveal that SG assembly is a component of the ANG- and tiRNA-induced stress response program.

摘要

血管生成素 (ANG) 是一种分泌型核糖核酸酶,可切割 tRNA,从而在哺乳动物细胞中启动应激反应程序。在这里,我们表明 ANG 抑制蛋白质合成并促进砷酸盐和 pateamine A 诱导的应激颗粒 (SG) 的组装。在用 ANG 抑制剂 RNH1 转染的细胞中,这些作用被消除。天然或合成的 5'-但不是 3'-tRNA 片段(tRNA 衍生的应激诱导 RNA;tiRNAs)的转染诱导 SG 的无磷酸化真核翻译起始因子 2alpha 独立组装。天然 5'-tiRNAs 但不是 3'-tiRNAs 带有 5'-单磷酸,这对于最佳 SG 组装是必需的。这些发现表明,SG 组装是 ANG 和 tiRNA 诱导的应激反应程序的一个组成部分。

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