Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly.
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.
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston,Massachusetts 02115, USA.
Mohamed M
MM
Emara
Pavel
P
Ivanov
Tyler
T
Hickman
Nemisha
N
Dawra
Sarah
S
Tisdale
Nancy
N
Kedersha
Guo-Fu
GF
Hu
Paul
P
Anderson
D018053:Arsenites / Q000494:pharmacology; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology*; D013723:Teratogens / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018053:Arsenites; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D015852:Eukaryotic Initiation Factor-2; D018942:Macrolides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C501467:RNH1 protein, human; D013723:Teratogens; D013844:Thiazoles; C421324:pateamine A; D012343:RNA, Transfer; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; C015001:arsenite