RNA editing is a physiological process and widespread in living organisms to produce various proteins with different functions from a single gene. In mammals, C or A of the RNA chain is base sequence-specifically hydrolytically deaminating, whereby C is replaced by U and A by I (inosine). Since I forms a Watson-Crick base pair with C, the genetic code is synonymous with G. These base conversions occur as a result of deamination of A or C, which has been found to be catalyzed by ADAR and APOBEC family enzymes. Recently, various techniques for RNA restoration by artificial RNA editing using ADARs have been reported. In this paper, we review recent findings regarding the application of ADARs to restoring the genetic code along with different approaches involved in the process of artificial RNA editing by ADAR. We have also addressed comparative studies of the various isoforms of ADARs. Therefore, we will try to provide a detailed overview of the artificial RNA editing and the role of ADAR with a focus on the enzymatic site directed A-to-I editing.
Most of artificial RNA editing systems use an active site of catalytic enzymes, ADARs, and a guide RNA complementary to the target to recruit an active site to the target RNA. One approach to artificial RNA editing is the use of chemical methods. Vogel and colleagues employed SNAP tag to join ADARs with a guide RNA and reported that the system is functional in vitro and in vivo. However, this technique requires a continuous supply of effector molecules to be effective. It is also known to use RNA-binding proteins to bind guide RNAs to enzymes. Two types of tethering system originating from bacteriophage are typically used in eukaryotes: the Lambda N system and MS2 system. Use of the ADAR enzyme with the MS2 system enables restoration of the genetic code, and holds promise for gene therapy.
In the future, site-directed A-to-I RNA editing including, enzymatic and non-enzymatic A-to-I editing, specially enzymatic, promises to effectively correct a variety of human diseases related to G to A mutations. A successful approach to treat the single mutation diseases will work as a potential remedy to the patients and will open a new era in this field of research.