RNA Editing and Modifications in Mood Disorders

Abstract

Major depressive disorder (MDD) is a major health problem with significant limitations in functioning and well-being. The World Health Organization (WHO) evaluates MDD as one of the most disabling disorders in the world and with very high social cost. Great attention has been given to the study of the molecular mechanism underpinning MDD at the genetic, epigenetic and proteomic level. However, the importance of RNA modifications has attracted little attention until now in this field. RNA molecules are extensively and dynamically altered by a variety of mechanisms. Similar to “epigenomic” changes, which modify DNA structure or histones, RNA alterations are now termed “epitranscriptomic” changes and have been predicted to have profound consequences for gene expression and cellular functionality. Two of these modifications, adenosine to inosine (A-to-I) RNA editing and m6A methylations, have fascinated researchers over the last years, showing a new level of complexity in gene expression. In this review, we will summary the studies that focus on the role of RNA editing and m6A methylation in MDD, trying to underline their potential breakthroughs and pitfalls.

The crosstalk between m6A RNA methylation and other epigenetic regulators: a novel perspective in epigenetic remodeling

“…The transition of A-to-I is processed by adenosine deaminases acting on RNA (ADAR) enzymes, which is a principal form of RNA editing 91 . It is reported that A-to-I is a key factor influencing RNA metabolism, such as miRNA processing 92 .…”

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

“…Upon DHT binding, the AR interacts specifically with ARE I/II in the promoter region of ADAR2 (adenosine deaminases acting on RNA), inducing its repression [ 77 ]. ADAR2 is an RNA editing gene that encodes an enzyme whose function is to modify adenosine nucleotide into inosine by deamination [ 78 ]. Repression of ADAR2 results in an increase in circFNTA levels, which leads to an elevated sponging of the miR-370-3p; this miRNA bind directly to the farnesyltransferase (FNTA) mRNA 3’ UTR binding site to increase FNTA expression.…”

Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?

“…It may possible that in hyper active brain areas, the overactive NMDA receptors might be the target of low therapeutic doses of ketamine because their affinity for ketamine might be higher (Shaffer et al, 2019). While little differences in the affinity for ketamine were reported for the four subtypes of NMDA receptors (Yamakura et al, 2000), it is also possible that in TRD subjects, the receptors undergoing turnover may acquire higher affinity for S-ketamine as a consequence of an editing process (Barbon and Magri, 2020). It has been reported that the turnover of AMPA receptors may be stimulated by ketamine and by its metabolites (2R,6R)-HNK and (2S,6S)-HNK (Zanos et al, 2016;Ho et al, 2018).…”