title: Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin to control growth and survival.
abstract: Angiogenin (ANG) promotes cell growth and survival. Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription. When cells are stressed, ANG mediates the production of tRNA-derived stress-induced small RNA (tiRNA), which reprograms protein translation into a survival mechanism. The ribonucleolytic activity of ANG is essential for both processes but how this activity is regulated is unknown. We report here that ribonuclease/angiogenin inhibitor 1 (RNH1) controls both the localization and activity of ANG. Under growth conditions, ANG is located in the nucleus and is not associated with RNH1 so that the ribonucleolytic activity is retained to ensure rRNA transcription. Cytoplasmic ANG is associated with and inhibited by RNH1 so that random cleavage of cellular RNA is prevented. Under stress conditions, ANG is localized to the cytoplasm and is concentrated in stress granules where it is not associated with RNH1 and thus remains enzymatically active for tiRNA production. By contrast, nuclear ANG is associated with RNH1 in stressed cells to ensure that the enzymatic activity is inhibited and no unnecessary rRNA is produced to save anabolic energy. Knockdown of RNH1 abolished stress-induced relocalization of ANG and decreased cell growth and survival.
authors.affiliation: Department of Biology, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, via Cintia, Naples 80126, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Pizzo
authors.forename: Carmen
authors.initials: C
authors.lastname: Sarcinelli
authors.forename: Jinghao
authors.initials: J
authors.lastname: Sheng
authors.forename: Sabato
authors.initials: S
authors.lastname: Fusco
authors.forename: Fabio
authors.initials: F
authors.lastname: Formiggini
authors.forename: Paolo
authors.initials: P
authors.lastname: Netti
authors.forename: Wenhao
authors.initials: W
authors.lastname: Yu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Alessio
authors.forename: Guo-Fu
authors.initials: GF
authors.lastname: Hu
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D006367:HeLa Cells; D006801:Humans; D018384:Oxidative Stress; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D002352:Carrier Proteins; C501467:RNH1 protein, human; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Angiogenin; RNH1; Stress granules