Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity

RNA editing is an important co- and post-transcriptional event that generates RNA and protein diversity. Aminoglycosides are a group of bactericidal antibiotics and a mainstay of antimicrobial therapy for several life-threatening infections. However, aminoglycosides can induce ototoxicity, resulting...

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Main Authors: Sijia Yan, Yulan Lu, Lin He, Xinzhi Zhao, Lihua Wu, Huizhong Zhu, Menglin Jiang, Yu Su, Wei Cao, Weidong Tian, Qinghe Xing
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fphar.2017.00854/full
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author Sijia Yan
Yulan Lu
Lin He
Lin He
Xinzhi Zhao
Lihua Wu
Huizhong Zhu
Menglin Jiang
Yu Su
Wei Cao
Weidong Tian
Qinghe Xing
author_facet Sijia Yan
Yulan Lu
Lin He
Lin He
Xinzhi Zhao
Lihua Wu
Huizhong Zhu
Menglin Jiang
Yu Su
Wei Cao
Weidong Tian
Qinghe Xing
author_sort Sijia Yan
collection DOAJ
description RNA editing is an important co- and post-transcriptional event that generates RNA and protein diversity. Aminoglycosides are a group of bactericidal antibiotics and a mainstay of antimicrobial therapy for several life-threatening infections. However, aminoglycosides can induce ototoxicity, resulting in damage to the organs responsible for hearing and balance. At low concentrations, aminoglycosides can bind to many RNA sequences and critically influence RNA editing. We used a bioinformatics approach to investigate the effect of aminoglycosides on global mRNA editing events to gain insight into the interactions between mRNA editing and aminoglycoside ototoxicity. We identified 6,850 mRNA editing sites in protein coding genes in embryonic zebrafish, and in about 10% of these, the degree of RNA editing changed more than 15% under aminoglycosides treatment. Twelve ear-development or ototoxicity related genes, including plekhm1, fgfr1a, sox9a, and calrl2, exhibited remarkable changes in mRNA editing levels in zebrafish treated with aminoglycosides. Our results indicate that aminoglycosides may have a widespread and complicated influence on the progress of mRNA editing and expression. Furthermore, these results highlight the potential importance of mRNA editing in the pathogenesis and etiology of aminoglycoside-induced ototoxicity.
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spelling doaj.art-19bd92372577421d8ab7b6041af828852022-12-21T17:49:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-11-01810.3389/fphar.2017.00854301120Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in OtotoxicitySijia Yan0Yulan Lu1Lin He2Lin He3Xinzhi Zhao4Lihua Wu5Huizhong Zhu6Menglin Jiang7Yu Su8Wei Cao9Weidong Tian10Qinghe Xing11Institutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, ChinaChildren's Hospital, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaInstitutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, ChinaZhengzhou People's Hospital, Zhengzhou, ChinaInstitutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, ChinaZhengzhou Central Hospital, Zhengzhou University, Zhengzhou, ChinaDepartment of Biostatistics and Computational Biology, School of Life Science, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, ChinaRNA editing is an important co- and post-transcriptional event that generates RNA and protein diversity. Aminoglycosides are a group of bactericidal antibiotics and a mainstay of antimicrobial therapy for several life-threatening infections. However, aminoglycosides can induce ototoxicity, resulting in damage to the organs responsible for hearing and balance. At low concentrations, aminoglycosides can bind to many RNA sequences and critically influence RNA editing. We used a bioinformatics approach to investigate the effect of aminoglycosides on global mRNA editing events to gain insight into the interactions between mRNA editing and aminoglycoside ototoxicity. We identified 6,850 mRNA editing sites in protein coding genes in embryonic zebrafish, and in about 10% of these, the degree of RNA editing changed more than 15% under aminoglycosides treatment. Twelve ear-development or ototoxicity related genes, including plekhm1, fgfr1a, sox9a, and calrl2, exhibited remarkable changes in mRNA editing levels in zebrafish treated with aminoglycosides. Our results indicate that aminoglycosides may have a widespread and complicated influence on the progress of mRNA editing and expression. Furthermore, these results highlight the potential importance of mRNA editing in the pathogenesis and etiology of aminoglycoside-induced ototoxicity.http://journal.frontiersin.org/article/10.3389/fphar.2017.00854/fullzebrafishRNA-editingRNA-Seqaminoglycosides (AG)ototoxicity
spellingShingle Sijia Yan
Yulan Lu
Lin He
Lin He
Xinzhi Zhao
Lihua Wu
Huizhong Zhu
Menglin Jiang
Yu Su
Wei Cao
Weidong Tian
Qinghe Xing
Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity
Frontiers in Pharmacology
zebrafish
RNA-editing
RNA-Seq
aminoglycosides (AG)
ototoxicity
title Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity
title_full Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity
title_fullStr Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity
title_full_unstemmed Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity
title_short Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity
title_sort dynamic editome of zebrafish under aminoglycosides treatment and its potential involvement in ototoxicity
topic zebrafish
RNA-editing
RNA-Seq
aminoglycosides (AG)
ototoxicity
url http://journal.frontiersin.org/article/10.3389/fphar.2017.00854/full
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