pateamine-a and angiogenin

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.

Topics: Arsenites; Blotting, Western; Bone Neoplasms; Carrier Proteins; Cells, Cultured; Cytoplasmic Granules; Enzyme Inhibitors; Epoxy Compounds; Eukaryotic Initiation Factor-2; Fluorescent Antibody Technique; Humans; Macrolides; Osteosarcoma; Oxidative Stress; Phosphorylation; Protein Biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease, Pancreatic; RNA, Messenger; RNA, Small Interfering; RNA, Transfer; Teratogens; Thiazoles; Tumor Cells, Cultured