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Proteome-Wide Analysis of ADAR-Mediated Messenger RNA Editing during Fruit Fly Ontogeny.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-08-31 , DOI: 10.1021/acs.jproteome.0c00347
Anna A Kliuchnikova 1, 2 , Anton O Goncharov 1, 3 , Lev I Levitsky 4 , Mikhail A Pyatnitskiy 1, 3 , Svetlana E Novikova 3 , Ksenia G Kuznetsova 1 , Mark V Ivanov 4 , Irina Y Ilina 1 , Tatyana E Farafonova 3 , Victor G Zgoda 3, 5 , Mikhail V Gorshkov 4 , Sergei A Moshkovskii 1, 2
Affiliation  

Adenosine-to-inosine RNA editing is an enzymatic post-transcriptional modification which modulates immunity and neural transmission in multicellular organisms. In particular, it involves editing of mRNA codons with the resulting amino acid substitutions. We identified such sites for developmental proteomes of Drosophila melanogaster at the protein level using available data for 15 stages of fruit fly development from egg to imago and 14 time points of embryogenesis. In total, 40 sites were obtained, each belonging to a unique protein, including four sites related to embryogenesis. The interactome analysis has revealed that the majority of the editing-recoded proteins were associated with synaptic vesicle trafficking and actomyosin organization. Quantitation data analysis suggested the existence of a phase-specific RNA editing regulation with yet unknown mechanisms. These findings supported the transcriptome analysis results, which showed that a burst in the RNA editing occurs during insect metamorphosis from pupa to imago. Finally, targeted proteomic analysis was performed to quantify editing-recoded and genomically encoded versions of five proteins in brains of larvae, pupae, and imago insects, which showed a clear tendency toward an increase in the editing rate for each of them. These results will allow a better understanding of the protein role in physiological effects of RNA editing.

中文翻译:

果蝇个体发育过程中 ADAR 介导的信使 RNA 编辑的全蛋白质组分析。

腺苷到肌苷 RNA 编辑是一种酶促转录后修饰,可调节多细胞生物体的免疫和神经传递。特别是,它涉及对 mRNA 密码子的编辑以及由此产生的氨基酸取代。我们确定了黑腹果蝇发育蛋白质组的这些位点在蛋白质水平上,使用从卵到成虫的 15 个果蝇发育阶段和胚胎发生的 14 个时间点的可用数据。总共获得了 40 个位点,每个位点属于一个独特的蛋白质,包括四个与胚胎发生相关的位点。相互作用组分析表明,大多数编辑记录的蛋白质与突触小泡运输和肌动球蛋白组织有关。定量数据分析表明存在一种特定于阶段的 RNA 编辑调节,但机制尚不清楚。这些发现支持了转录组分析结果,表明在昆虫从蛹到成虫的变态过程中发生了 RNA 编辑的爆发。最后,进行了靶向蛋白质组学分析,以量化幼虫大脑中五种蛋白质的编辑编码和基因组编码版本,蛹和成虫,它们显示出明显的趋势,即它们各自的编辑率都有增加的趋势。这些结果将有助于更好地理解蛋白质在 RNA 编辑生理效应中的作用。
更新日期:2020-10-02
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