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, as a result of the reaction, adenosine is converted to inosine in particular sites of RNA. In case of messenger RNA, during translation, inosine is recognized as guanine leading to amino acid substitutions. Those substitutions are shown to affect substantially the function of proteins, e.g. subunits of the glutamate receptor. Nevertheless, most of the works on RNA editing use analysis of nucleic acids, even those which deal with a coding RNA. 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 will directly conduct a qualitative and quantitative analysis of protein edited sequences in the scale of whole proteome.