Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity.
Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity.
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氨基糖苷类药物处理下斑马鱼的动态编辑及其与耳毒性的潜在关系
DOI：
10.3389/fphar.2017.00854
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发表时间：
2017
影响因子：
5.6
通讯作者：
Xing Q
中科院分区：
文献类型：
--
作者：
Yan S;Lu Y;He L;Zhao X;Wu L;Zhu H;Jiang M;Su Y;Cao W;Tian W;Xing Q
RNA编辑是产生RNA和蛋白质多样性的重要的协同和转录后事件。氨基糖苷类抗生素是一组杀菌抗生素，是几种危及生命的感染的主要抗菌治疗手段。然而，氨基糖苷类药物会引起耳毒性，对负责听力和平衡的器官造成损害。在低浓度下，氨基糖苷类化合物可以与许多RNA序列结合，并严重影响RNA的编辑。我们使用生物信息学的方法来研究氨基糖苷类药物对全球信使核糖核酸编辑事件的影响，以深入了解信使核糖苷编辑和氨基糖苷类耳毒性之间的相互作用。我们在斑马鱼胚胎蛋白质编码基因中确定了6850个RNA编辑点，其中约10%的斑马鱼在氨基糖苷类药物处理下RNA编辑度变化了15%以上。12个与耳朵发育或耳毒性相关的基因，包括plekhm1、fgfr1a、sox9a和calrl2，在氨基糖苷类处理的斑马鱼中表现出显著的mRNA编辑水平的变化。我们的结果表明，氨基糖苷类化合物可能对mRNA的编辑和表达过程产生广泛而复杂的影响。此外，这些结果强调了mRNA编辑在氨基糖苷类耳毒性的发病机制和病因学中的潜在重要性。
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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影响因子：
3.8
作者：
Karasawa, Takatoshi;Wang, Qi;Steyger, Peter S.
通讯作者：
Steyger, Peter S.
影响因子：
2.5
作者：
Head, Jeffery R.;Gacioch, Leah;Meyers, Jason R.
通讯作者：
Meyers, Jason R.
影响因子：
12.3
作者：
Danecek P;Nellåker C;McIntyre RE;Buendia-Buendia JE;Bumpstead S;Ponting CP;Flint J;Durbin R;Keane TM;Adams DJ
通讯作者：
Adams DJ
影响因子：
3.1
作者：
Pozo P;Hoopengardner B
通讯作者：
Hoopengardner B
影响因子：
4.6
作者：
Dorsky, RI;Itoh, M;Chitnis, A
通讯作者：
Chitnis, A