RNA editing in the forefront of epitranscriptomics and human health

Abstract

Post-transcriptional modifications have been recently expanded with the addition of RNA editing, which is predominantly mediated by adenosine and cytidine deaminases acting on DNA and RNA. Here, we review the full spectrum of physiological processes in which these modifiers are implicated, among different organisms. Adenosine to inosine (A-to-I) editors, members of the ADAR and ADAT protein families are important regulators of alternative splicing and transcriptional control. On the other hand, cytidine to uridine (C-to-U) editors, members of the AID/APOBEC family, are heavily implicated in innate and adaptive immunity with important roles in antibody diversification and antiviral response. Physiologically, these enzymes are present in the nucleus and/or the cytoplasm, where they modify various RNA molecules, including miRNAs, tRNAs apart from mRNAs, whereas DNA editing is also possible by some of them. The expansion of next generation sequencing technologies provided a wealth of data regarding such modifications. RNA editing has been implicated in various disorders including cancer, and neurological diseases of the brain or the central nervous system. It is also related to cancer heterogeneity and the onset of carcinogenesis. Response to treatment can also be affected by the RNA editing status where drug efficacy is significantly compromised. Studying RNA editing events can pave the way to the identification of new disease biomarkers, and provide a more personalised therapy to various diseases.

Sex-Dependent RNA Editing and N6-adenosine RNA Methylation Profiling in the Gonads of a Fish, the Olive Flounder (Paralichthys olivaceus)

“…RNA editing and m6A have been recognized as targets for drug discovery, and some drugs for inhibiting RNA editing enzymes or m6A modification regulators were discovered recently (Christofi and Zaravinos, 2019;Ianniello et al, 2019). Our study showed the levels of the RNA editing and m6A were different in the flounder ovary and testis, and some sex-related genes (e.g., dmrt1, amh, and wt1) may be regulated by RNA modifications.…”

Hypermutation in single-stranded DNA

“…The latter can work on DNA as well as on RNA. RNA editing of a small number of specific sites is a well-known phenomenon with physiological function, however widespread editing of random sites in mRNAs is occurring at a low frequency in each transcript (reviewed in [104,105]. RNA editing by ADARs [106,107] and APOBECs [108] was suggested to play a role in viral evolution and restriction in cells.…”

Zoonotic and reverse zoonotic events of SARS-CoV-2 and their impact on global health

“…cytosolic DNA). It is noteworthy that a subset of ISG, such as RNA-dependent adenosine deaminases (ADARs) and apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) family genes, promote mutations in the viral RNA leading to the emergence of novel viral strains, and at the same time attenuating host's innate immune responses to viral RNA [31,32]. Thus, the persistence of viral infections, increased RNA editing, and longer life span of bats increase the probability of viral mutations and recombination events, which potentially contribute to the emergence of infectious and pathogenic CoV strains for other species.…”