Knockout of Drosophila RNase ZL impairs mitochondrial transcript processing, respiration and cell cycle progression.
Nucleic Acids Res
; 43(21): 10364-75, 2015 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-26553808
ABSTRACT
RNase Z(L) is a highly conserved tRNA 3'-end processing endoribonuclease. Similar to its mammalian counterpart, Drosophila RNase Z(L) (dRNaseZ) has a mitochondria targeting signal (MTS) flanked by two methionines at the N-terminus. Alternative translation initiation yields two protein forms the long one is mitochondrial, and the short one may localize in the nucleus or cytosol. Here, we have generated a mitochondria specific knockout of the dRNaseZ gene. In this in vivo model, cells deprived of dRNaseZ activity display impaired mitochondrial polycistronic transcript processing, increased reactive oxygen species (ROS) and a switch to aerobic glycolysis compensating for cellular ATP. Damaged mitochondria impose a cell cycle delay at the G2 phase disrupting cell proliferation without affecting cell viability. Antioxidants attenuate genotoxic stress and rescue cell proliferation, implying a critical role for ROS. We suggest that under a low-stress condition, ROS activate tumor suppressor p53, which modulates cell cycle progression and promotes cell survival. Transcriptional profiling of p53 targets confirms upregulation of antioxidant and cycB-Cdk1 inhibitor genes without induction of apoptotic genes. This study implicates Drosophila RNase Z(L) in a novel retrograde signaling pathway initiated by the damage in mitochondria and manifested in a cell cycle delay before the mitotic entry.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ciclo Celular
/
Processamento Pós-Transcricional do RNA
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Proteínas de Drosophila
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Endorribonucleases
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Mitocôndrias
Limite:
Animals
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos