Abstract
A-to-I RNA editing is a post-transcriptional modification that converts adenosines to inosines in both coding and noncoding RNA transcripts. It is catalyzed by ADAR (adenosine deaminase acting on RNA) enzymes, which exist throughout the body but are most prevalent in the central nervous system. Inosines exhibit properties that are most similar to those of guanosines. As a result, ADAR-mediated editing can post-transcriptionally alter codons, introduce or remove splice sites, or affect the base pairing of the RNA molecule with itself or with other RNAs. A-to-I editing is a mechanism that regulates and diversifies the transcriptome, but the full biological significance of ADARs is not understood. ADARs are highly conserved across vertebrates and are essential for normal development in mammals. Aberrant ADAR activity has been associated with a wide range of human diseases, including cancer, neurological disorders, metabolic diseases, viral infections and autoimmune disorders. ADARs have been shown to contribute to disease pathologies by editing of glutamate receptors, editing of serotonin receptors, mutations in ADAR genes, and by other mechanisms, including recently identified regulatory roles in microRNA processing. Advances in research into many of these diseases may depend on an improved understanding of the biological functions of ADARs. Here, we review recent studies investigating connections between ADAR-mediated RNA editing and human diseases.
Highlights
adenosine to inosine (A-to-I) RNA editing is a post-transcriptional modification that converts adenosines to inosines in both coding and noncoding RNA transcripts
A-to-I editing, which is catalyzed by enzymes of the adenosine deaminase acting on RNA (ADAR) family, is most prevalent in the central nervous system (CNS) but occurs in many tissues [1,2,3]
ADAR1 and ADAR2 are present in many tissues, whereas ADAR3 is expressed in brain tissues and is believed to be catalytically inactive [1,9]
Summary
It has been established that changes in A-to-I editing are involved in a range of human diseases. Editing events that affect repetitive RNA sequences or other noncoding regions generally serve an unknown function, and it remains to be seen if they play a role in the pathology of human diseases. ADARs edit such a large number of RNA substrates that ADAR activity seems likely to be involved, directly or indirectly, in many cellular processes. A novel study recently demonstrated the potential of specific RNAinteracting proteins to act as substrate-specific inhibitors of ADAR enzymes [84] This highlights the importance of improving our understanding of the molecular pathways involved in ADAR-related human diseases. Competing interests The authors declare that they have no competing interests
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