Sarcinelli, Carmen (2013) Ribonuclease/angiogenin inhibitor 1 and angiogenin: regulation of their intracellular localization in stress response. [Tesi di dottorato] (Unpublished)

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Item Type: Tesi di dottorato
Lingua: English
Title: Ribonuclease/angiogenin inhibitor 1 and angiogenin: regulation of their intracellular localization in stress response
Creators:
CreatorsEmail
Sarcinelli, Carmencarmen.sarcinelli@unina.it
Date: 29 March 2013
Number of Pages: 62
Institution: Università degli Studi di Napoli Federico II
Department: Biologia strutturale e funzionale
Scuola di dottorato: Scienze biologiche
Dottorato: Biochimica e biologia cellulare e molecolare
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
nomeemail
Arcari, Paolopaolo.arcari@unina.it
Tutor:
nomeemail
Pizzo, Eliodoroelipizzo@unina.it
Date: 29 March 2013
Number of Pages: 62
Uncontrolled Keywords: Stress granules Angiogenin RNH1
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Date Deposited: 10 Apr 2013 15:51
Last Modified: 17 Jun 2014 06:04
URI: http://www.fedoa.unina.it/id/eprint/9216

Abstract

Under stress conditions eukaryotic cells activate an integrate response pathway to modulate cell metabolism. A hallmark of the stress response is transient formation of ribonucleo-protein cytoplasmic foci named stress granules (SGs) to protect translationally silenced mRNA. Regard to stress response, notable is the role of angiogenin (ANG), a member of the Vertebrate Ribonuclease Superfamily. Under growth conditions, ANG undergoes nuclear translocation and is accumulated in nucleolus where it stimulates ribosomal RNA (rRNA) transcription. When cells are stressed, ANG mediates the production of cytoplasmic tRNA-derived stress-induced small RNA (tiRNA) that suppress global protein translation and promote cell survival. It is unknown where ANG is localized in stressed cells and how ANG activities are regulated in the cell under different growth conditions. In this study it has been reported that ANG is localized in stress granules (SGs) when cells are stressed and that its localization as well as its activities are regulated by ribonuclease/angiogenin inhibitor 1 (RNH1), that binds ANG with an affinity in femtomolar range. Under growth conditions, ANG is mainly located in the nucleus where it is not associated with RNH1 so that ANG is able to stimulate rRNA transcription. Whereas cytoplasmic ANG traces are associated with RNH1 to avoid accordingly random RNA degradation. Under stress conditions, ANG leaves nuclear compartment to become mainly localized in the cytoplasm especially concentrated in SGs. Extremely intriguing, although RNH1 is also recruited to SGs, RNH1 and ANG are not physically associated in SGs so that ANG is able to keep its enzymatic activity. In contrast, nuclear ANG traces are inhibited by RNH1 in stressed cells maybe to preserve anabolic energy needed to the cell. Subcellular distribution pattern of RNH1 under different growth conditions is opposite. Under stress conditions, RNH1 is accumulated in nuclear compartment, whereas its cytoplasmic level is reduced and in the same time it is also recruited to SGs. These results demonstrate that subcellular localization of ANG and RNH1 is dynamic and dependent on the growth status of the cell. Moreover, knockdown of RNH1 abolishes stress-induced localization of ANG to SGs and decrease cell survival under stress so that RNH1 regulates ANG localization in both growth and stress conditions and control growth and survival behaviours.

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