Adenosine-to-Inosine RNA Editing in Mouse and Human Brain Proteomes

Abstract

Proteogenomics is based on the use of customized genome or RNA sequencing databases for interrogation of shotgun proteomics data in search for proteome-level evidence of genome variations or RNA editing. In this work, the products of adenosine-to-inosine RNA editing in human and murine brain proteomes are identified using publicly available brain proteome LC-MS/MS datasets and an RNA editome database compiled from several sources. After filtering of false-positive results, 20 and 37 sites of editing in proteins belonging to 14 and 32 genes are identified for murine and human brain proteomes, respectively. Eight sites of editing identified with high spectral counts overlapped between human and mouse brain samples. Some of these sites have been previously reported using orthogonal methods, such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors, CYFIP2, coatomer alpha. Also, differential editing between neurons and microglia is demonstrated in this work for some of the proteins from primary murine brain cell cultures. Because many edited sites are still not characterized functionally at the protein level, the results provide a necessary background for their further analysis in normal and diseased cells and tissues using targeted proteomic approaches.

Keywords: AMPA glutamate receptor; adenosine deaminase; brain proteome; proteogenomics; ribonucleic acid (RNA) editing.