# Unraveling ADAR-Mediated Protein Recoding: A Proteogenomic Exploration in Model Organisms and Human Pathology

## TL;DR

This study explores how ADAR enzymes edit RNA to change proteins, focusing on nervous systems and tumors in various organisms including humans.

## Contribution

The study provides a proteogenomic validation of ADAR-mediated protein recoding and identifies its impact on cytoskeletal and synaptic proteins.

## Key findings

- Proteogenomic analysis identified dozens of ADAR-mediated protein recoding events in model organisms and humans.
- Recoding events primarily affect cytoskeletal and synaptic transmission proteins across species.
- Protein recoding levels are not directly linked to ADAR enzyme abundance or target protein levels.

## Abstract

This paper summarizes the results of multi-year studies performed by our research team, focusing on an analysis of protein recoding mediated by messenger RNA editing by ADAR adenosine deaminases. Searching for ADAR-mediated protein recoding was performed in the central nervous system of the model organisms, fruit fly and mouse, as well as in the human proteomic datasets. The proteogenomic approach has made it possible to identify dozens of editing events in the proteome, thus validating the results of transcriptomic studies. The observed recoding events in animals, ranging from insects to mammals, mainly affect the cytoskeletal components and proteins involved in synaptic transmission. In humans, recoding changes are most often observed in the central nervous system or tumor tissues. Over 15 million editing sites have been identified in humans; only a few thousand of those can potentially yield amino acid substitutions. Using a proteogenomic approach, dozens of protein recoding sites are identified, demonstrating their origin in ADAR RNA editing. Moreover, this revealed that the level of recoding at specific sites is not directly related to the abundance of ADAR enzymes per se or their target proteins. The recoding processes probably have differential regulation of interactions at the mRNA level that is yet to be clarified.