Key result
RNA editing by ADAR enzymes influences cancer progression via immunosuppression and alters neurotransmitter receptor functions in the central nervous system.
Why the study?
RNA editing by adenosine deaminases of the ADAR family is of growing interest in cancer and other human diseases, prompting a review of current concepts on the functions of two active mammalian ADAR isoforms.
This review highlights the dual roles of ADAR enzymes in promoting cancer progression via immunosuppression and potentially activating antitumor immunity through neoantigen formation.
ADAR editing may shape cancer immunity and CNS signaling; leaves open therapeutic targeting pending prospective validation.
RNA editing by adenosine deaminases of the ADAR family attracts a growing interest of researchers, both zoologists studying ecological and evolutionary plasticity of invertebrates and medical biochemists focusing on the mechanisms of cancer and other human diseases. These enzymes deaminate adenosine residues in the double-stranded (ds) regions of RNA with the formation of inosine. As a result, some RNAs change their three-dimensional structure and functions. Adenosine-to-inosine editing in the mRNA coding sequences may cause amino acid substitutions in the encoded proteins. Here, we reviewed current concepts on the functions of two active ADAR isoforms identified in mammals (including humans). The ADAR1 protein, which acts non-specifically on extended dsRNA regions, is capable of immunosuppression via inactivation of the dsRNA interactions with specific sensors inducing the cell immunity. Expression of a specific ADAR1 splicing variant is regulated by the type I interferons by the negative feedback mechanism. It was shown that immunosuppressing effects of ADAR1 facilitate progression of some types of cancer. On the other hand, changes in the amino acid sequences resulting from the mRNA editing by the ADAR enzymes can result in the formation of neoantigens that can activate the antitumor immunity. The ADAR2 isoform acts on RNA more selectively; its function is associated with the editing of mRNA coding regions and can lead to the amino acid substitutions, in particular, those essential for the proper functioning of some neurotransmitter receptors in the central nervous system.
No takes yet. Share an insight, caveat, or question.
Goncharov et al. (2019) conducted a review in Cancer and neurological functions. RNA editing by ADAR adenosine deaminases was evaluated. RNA editing by ADAR enzymes influences cancer progression via immunosuppression and alters neurotransmitter receptor functions in the central nervous system.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: