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Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression
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 lon...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666369/ https://www.ncbi.nlm.nih.gov/pubmed/26553808 http://dx.doi.org/10.1093/nar/gkv1149 |
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author | Xie, Xie Dubrovsky, Edward B. |
author_facet | Xie, Xie Dubrovsky, Edward B. |
author_sort | Xie, Xie |
collection | PubMed |
description | 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 G(2) 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. |
format | Online Article Text |
id | pubmed-4666369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-46663692015-12-02 Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression Xie, Xie Dubrovsky, Edward B. Nucleic Acids Res Molecular Biology 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 G(2) 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. Oxford University Press 2015-12-02 2015-11-08 /pmc/articles/PMC4666369/ /pubmed/26553808 http://dx.doi.org/10.1093/nar/gkv1149 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular Biology Xie, Xie Dubrovsky, Edward B. Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression |
title | Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression |
title_full | Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression |
title_fullStr | Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression |
title_full_unstemmed | Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression |
title_short | Knockout of Drosophila RNase Z(L) impairs mitochondrial transcript processing, respiration and cell cycle progression |
title_sort | knockout of drosophila rnase z(l) impairs mitochondrial transcript processing, respiration and cell cycle progression |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666369/ https://www.ncbi.nlm.nih.gov/pubmed/26553808 http://dx.doi.org/10.1093/nar/gkv1149 |
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