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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Arsenites / pharmacology
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Blotting, Western
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Bone Neoplasms / genetics
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Bone Neoplasms / metabolism
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Bone Neoplasms / pathology*
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Carrier Proteins / pharmacology
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Cells, Cultured
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Cytoplasmic Granules / metabolism*
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Enzyme Inhibitors / pharmacology
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Epoxy Compounds / pharmacology
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Eukaryotic Initiation Factor-2 / antagonists & inhibitors
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Eukaryotic Initiation Factor-2 / metabolism
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Fluorescent Antibody Technique
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Humans
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Macrolides / pharmacology
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Osteosarcoma / genetics
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Osteosarcoma / metabolism
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Osteosarcoma / pathology*
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Oxidative Stress
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Phosphorylation / drug effects
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Protein Biosynthesis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / pharmacology
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RNA, Transfer / chemistry
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RNA, Transfer / genetics
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RNA, Transfer / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Ribonuclease, Pancreatic / pharmacology*
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Teratogens / pharmacology
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Thiazoles / pharmacology
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Tumor Cells, Cultured
Substances
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Arsenites
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Carrier Proteins
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Enzyme Inhibitors
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Epoxy Compounds
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Eukaryotic Initiation Factor-2
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Macrolides
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RNA, Messenger
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RNA, Small Interfering
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RNH1 protein, human
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Teratogens
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Thiazoles
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pateamine A
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RNA, Transfer
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angiogenin
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Ribonuclease, Pancreatic
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arsenite