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

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.