Proteome-Wide Analysis of ADAR-Mediated Messenger RNA Editing during Fruit Fly Ontogeny

• Published in: Journal of proteome research Vol. 19; no. 10; pp. 4046 - 4060
• Main Authors: Kliuchnikova, Anna A, Goncharov, Anton O, Levitsky, Lev I, Pyatnitskiy, Mikhail A, Novikova, Svetlana E, Kuznetsova, Ksenia G, Ivanov, Mark V, Ilina, Irina Y, Farafonova, Tatyana E, Zgoda, Victor G, Gorshkov, Mikhail V, Moshkovskii, Sergei A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.10.2020
• Subjects: Adenosine Deaminase - genetics; Adenosine Deaminase - metabolism; Animals; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Inosine - metabolism; Proteome - genetics; Proteome - metabolism; Proteomics; RNA Editing; RNA, Messenger - genetics; proteoform; RNA editing; adenosine deaminase; ontogeny; Drosophila melanogaster; RNA dependent; proteome
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.0c00347

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.