PT - JOURNAL ARTICLE AU - Ksenia G. Kuznetsova AU - Anna A. Kliuchnikova AU - Irina I. Ilina AU - Alexey L. Chernobrovkin AU - Svetlana E. Novikova AU - Tatyana E. Farafonova AU - Dmitry S. Karpov AU - Mark V. Ivanov AU - Anton O. Goncharov AU - Ekaterina V. Ilgisonis AU - Olga E. Voronko AU - Shamsudin S. Nasaev AU - Victor G. Zgoda AU - Roman A. Zubarev AU - Mikhail V. Gorshkov AU - Sergei A. Moshkovskii TI - Proteogenomics of adenosine-to-inosine RNA editing in the fruit fly AID - 10.1101/101949 DP - 2018 Jan 01 TA - bioRxiv PG - 101949 4099 - http://biorxiv.org/content/early/2018/06/29/101949.short 4100 - http://biorxiv.org/content/early/2018/06/29/101949.full AB - Adenosine-to-inosine RNA editing is one of the most common types of RNA editing, a posttranscriptional modification made by special enzymes. We present a proteomic study on this phenomenon for Drosophila melanogaster. Three proteome data sets were used in the study: two taken from public repository and the third one obtained here. A customized protein sequence database was generated using results of genome-wide adenosine-to-inosine RNA studies and applied for identifying the edited proteins. The total number of 68 edited peptides belonging to 59 proteins was identified in all data sets. Eight of them being shared between the whole insect, head and brain proteomes. Seven edited sites belonging to synaptic vesicle and membrane trafficking proteins were selected for validation by orthogonal analysis by Multiple Reaction Monitoring. Five editing events in cpx, Syx1A, Cadps, CG4587 and EndoA were validated in fruit fly brain tissue at the proteome level using isotopically labeled standards. Ratios of unedited-to-edited proteoforms varied from 35:1 (Syx1A) to 1:2 (EndoA). Lys-137 to Glu editing of endophilin A may have functional consequences for its interaction to membrane. The work demonstrates the feasibility to identify the RNA editing event at the proteome level using shotgun proteomics and customized edited protein database.