Abstract
RNA epigenetics is perhaps the most recent field of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combinations whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes in RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.
Highlights
Translational epigenetics is a relatively new branch of molecular biology that investigates regulatory processes occurring molecularly “above” the primary DNA sequence associated with physiological and pathophysiological conditions
The field of epigenetics is rushing forward, most of the epigenetic studies on Cardiovascular diseases (CVDs) and/or chronic diseases are still focused on DNA methylation [80], histone code modifications [81], and the regulation of protein expression and function by a plethora of non-coding RNAs (ncRNAs) [82] rather than on the quality, quantity, and role of RNA epigenetic modifications
Recent literature highlighted the controversial role of RNA methylation, occurring mainly on adenosines, and resulting in increased mRNA instability, repressed protein synthesis [42,45], or its stabilizing regulatory loops between mRNAs and lncRNAs [39,42,44,61]
Summary
Translational epigenetics is a relatively new branch of molecular biology that investigates regulatory processes occurring molecularly “above” the primary DNA sequence associated with physiological and pathophysiological conditions. Several reviews have been written about the regulatory role of ncRNAs [14,15,16,17], our knowledge is still limited about epigenetic modifications occurring in ncRNAs in physiological and pathological conditions It is well known, that RNA sequences can be the target of methyltransferases such as N6-adenosine methyltransferase-like 3 (METTL3). Methyl groups can be added on riboguanosine too, in particular at position 7 generating 7-methylguanosine (m7G) [29] This modification mainly occurs on capped [30] and recapped mRNAs and is mediated by canonical mRNA capping methyltransferase (RNMT), which regulates mRNA translation into proteins [31] (see Figure 3). For more detailed mechanistic insights, the readers will be directed to recent comprehensive reviews in which the molecular mechanism and biological functions are well described [32,33,34,35]
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