Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells
Abstract Background Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC3A edits many mRNAs in monocytes and macrophages in response to hypoxia...
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doaj-4cb51bbdf793402da1a28e36fd3f9e702020-11-25T02:37:32ZengBMCGenome Biology1474-760X2019-02-0120111710.1186/s13059-019-1651-1Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cellsShraddha Sharma0Jianmin Wang1Emad Alqassim2Scott Portwood3Eduardo Cortes Gomez4Orla Maguire5Per H. Basse6Eunice S. Wang7Brahm H. Segal8Bora E. Baysal9Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer CenterDepartment of Bioinformatics and Biostatistics, Roswell Park Comprehensive Cancer CenterDepartment of Internal Medicine, Roswell Park Comprehensive Cancer CenterDepartment of Medicine, Roswell Park Comprehensive Cancer CenterDepartment of Bioinformatics and Biostatistics, Roswell Park Comprehensive Cancer CenterDepartment of Flow and Image Cytometry, Roswell Park Comprehensive Cancer CenterDepartment of Medicine, Roswell Park Comprehensive Cancer CenterDepartment of Medicine, Roswell Park Comprehensive Cancer CenterDepartment of Internal Medicine, Roswell Park Comprehensive Cancer CenterDepartment of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer CenterAbstract Background Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC3A edits many mRNAs in monocytes and macrophages in response to hypoxia and interferons, the physiological significance of such editing is unclear. Results Here, we show that the related cytidine deaminase, APOBEC3G, induces site-specific C-to-U RNA editing in natural killer cells, lymphoma cell lines, and, to a lesser extent, CD8-positive T cells upon cellular crowding and hypoxia. In contrast to expectations from its anti-HIV-1 function, the highest expression of APOBEC3G is shown to be in cytotoxic lymphocytes. RNA-seq analysis of natural killer cells subjected to cellular crowding and hypoxia reveals widespread C-to-U mRNA editing that is enriched for genes involved in mRNA translation and ribosome function. APOBEC3G promotes Warburg-like metabolic remodeling in HuT78 T cells under similar conditions. Hypoxia-induced RNA editing by APOBEC3G can be mimicked by the inhibition of mitochondrial respiration and occurs independently of HIF-1α. Conclusions APOBEC3G is an endogenous RNA editing enzyme in primary natural killer cells and lymphoma cell lines. This RNA editing is induced by cellular crowding and mitochondrial respiratory inhibition to promote adaptation to hypoxic stress.http://link.springer.com/article/10.1186/s13059-019-1651-1RNA editingAPOBEC3NK cellsHypoxiaCell stressMitochondria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shraddha Sharma Jianmin Wang Emad Alqassim Scott Portwood Eduardo Cortes Gomez Orla Maguire Per H. Basse Eunice S. Wang Brahm H. Segal Bora E. Baysal |
spellingShingle |
Shraddha Sharma Jianmin Wang Emad Alqassim Scott Portwood Eduardo Cortes Gomez Orla Maguire Per H. Basse Eunice S. Wang Brahm H. Segal Bora E. Baysal Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells Genome Biology RNA editing APOBEC3 NK cells Hypoxia Cell stress Mitochondria |
author_facet |
Shraddha Sharma Jianmin Wang Emad Alqassim Scott Portwood Eduardo Cortes Gomez Orla Maguire Per H. Basse Eunice S. Wang Brahm H. Segal Bora E. Baysal |
author_sort |
Shraddha Sharma |
title |
Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells |
title_short |
Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells |
title_full |
Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells |
title_fullStr |
Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells |
title_full_unstemmed |
Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells |
title_sort |
mitochondrial hypoxic stress induces widespread rna editing by apobec3g in natural killer cells |
publisher |
BMC |
series |
Genome Biology |
issn |
1474-760X |
publishDate |
2019-02-01 |
description |
Abstract Background Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC3A edits many mRNAs in monocytes and macrophages in response to hypoxia and interferons, the physiological significance of such editing is unclear. Results Here, we show that the related cytidine deaminase, APOBEC3G, induces site-specific C-to-U RNA editing in natural killer cells, lymphoma cell lines, and, to a lesser extent, CD8-positive T cells upon cellular crowding and hypoxia. In contrast to expectations from its anti-HIV-1 function, the highest expression of APOBEC3G is shown to be in cytotoxic lymphocytes. RNA-seq analysis of natural killer cells subjected to cellular crowding and hypoxia reveals widespread C-to-U mRNA editing that is enriched for genes involved in mRNA translation and ribosome function. APOBEC3G promotes Warburg-like metabolic remodeling in HuT78 T cells under similar conditions. Hypoxia-induced RNA editing by APOBEC3G can be mimicked by the inhibition of mitochondrial respiration and occurs independently of HIF-1α. Conclusions APOBEC3G is an endogenous RNA editing enzyme in primary natural killer cells and lymphoma cell lines. This RNA editing is induced by cellular crowding and mitochondrial respiratory inhibition to promote adaptation to hypoxic stress. |
topic |
RNA editing APOBEC3 NK cells Hypoxia Cell stress Mitochondria |
url |
http://link.springer.com/article/10.1186/s13059-019-1651-1 |
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