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


Download (3MB) | Anteprima
[error in script] [error in script]
Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Ribonuclease/angiogenin inhibitor 1 and angiogenin: regulation of their intracellular localization in stress response
Data: 29 Marzo 2013
Numero di pagine: 62
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: 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:
Data: 29 Marzo 2013
Numero di pagine: 62
Parole chiave: Stress granules Angiogenin RNH1
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Depositato il: 10 Apr 2013 15:51
Ultima modifica: 17 Giu 2014 06:04


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.

Actions (login required)

Modifica documento Modifica documento