Angiogenin-induced tRNA-derived Stress-induced RNAs Promote Stress-induced Stress Granule Assembly
作者:Mohamed M. Emara, Pavel Ivanov, Tyler Hickman, Nemisha Dawra, Sarah Tisdale, Nancy Kedersha, Guo-fu Hu, Paul Anderson · 发表于:Journal of Biological Chemistry · 年份:2010 · DOI:10.1074/jbc.m109.077560 · 被引用次数:516 · 研究领域:RNA Research and Splicing、RNA modifications and cancer、RNA and protein synthesis mechanisms
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.