N6-Methyladenosine In Rna Of Atherosclerotic Plaques: An Epitranscriptomic Signature Of Human Carotid Atherosclerosis

Background: More than 170 post-transcriptional RNA modifications regulate the localization, processing and function of cellular RNAs, and aberrant RNA modifications have been linked to a range of human diseases. The RNA modification landscape in atherosclerosis, the main underlying cause of cardiovascular diseases, is still largely unknown.Methods: We used mass spectrometry to analyse a selection of RNA-modifying enzymes and the N6methyladenosine (m(6)A) in carotid atherosclerotic lesion samples representing early and advanced stages of atherosclerosis as compared to non-atherosclerotic arteries from healthy controls.Findings: (i) the detection of different levels of several enzymes involved in methylations occurring in rRNA and mRNA; (ii) these findings included changes in the levels of methyltransferases ('writers'), binding proteins ('readers') and demethylases ('erasers') during atherosclerosis as compared to nonatherosclerotic control arteries, with generally the most prominent differences in samples from early atherosclerotic lesions; and (iii) these changes were accompanied by a marked downregulation of m(6)A in rRNA, the most abundant and well-studied modification in mRNA with a wide range of effects on cell biology.Interpretation: We show for the first time that RNA-modifying enzymes and the well-studied RNA modification m(6)A are differentially regulated in atherosclerotic lesions, which potentially could help creating new prognostic and treatment strategies. (C) 2020 The Authors. Published by Elsevier Inc.