ADAR-mediated messenger RNA Editing: Analysis at the proteome level

Abstract

Post-transcriptional RNA editing by RNA-specific adenosine deaminases (ADAR) was discovered more than two decades ago. It provides additional regulation of animal and human transcriptome. In most cases, it occurs in nervous tissue where this results in conversion of adenosine to inosine at particular RNA sites. In the case of mRNA, an inosine residue is recognized by ribosome as guanine thus leading to amino acid substitutions during translation. Although such substitutions are shown to affect substantially functions of proteins (e.g. glutamate receptor) most of studies on RNA editing are mainly limited by analysis of nucleic acids even in the case of protein coding RNA transcripts. In this review, we propose the use of shotgun proteomics based on high resolution liquid chromatography and mass spectrometry for investigation of the effects of RNA editing at the protein level. Recently developed methods of big data processing allow combining the results of various omics techniques, being referred to as proteogenomics. The proposed proteogenomic approach for the analysis of RNA editing at the protein level is applicable for qualitative and quantitative analyses of protein edited sequences at the whole proteome level. Using this approach it will be possible to evaluate clinical importance of this phenomenon especially in the context of nervous system diseases.