N6-methyladenosine in RNA of atherosclerotic plaques: An epitranscriptomic signature of human carotid atherosclerosis.

Abstract

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 N6-methyladenosine (m6A) 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 non-atherosclerotic 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 m6A 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 m6A are differentially regulated in atherosclerotic lesions, which potentially could help creating new prognostic and treatment strategies.

• Authors: Ana Quiles-Jiménez, Ida Gregersen, Mirta Mittelstedt Leal de Sousa, Azhar Abbas, Xiang Yi Kong, Ingrun Alseth, Sverre Holm, Tuva B Dahl, Karolina Skagen, Mona Skjelland, Pål Aukrust, Magnar Bjørås, Bente Halvorsen
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 533 Issue 4 Pg. 631-637 (12 17 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 33004177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• RNA, Messenger
• RNA, Ribosomal
• N-methyladenosine
• Oxidoreductases, N-Demethylating
• Methyltransferases
• Adenosine

Topics

• Adenosine (analogs & derivatives, analysis, metabolism)
• Carotid Artery Diseases (enzymology, genetics, metabolism)
• Chromatography, Liquid
• Humans
• Methylation
• Methyltransferases (metabolism)
• Oxidoreductases, N-Demethylating (metabolism)
• Plaque, Atherosclerotic (enzymology, genetics, metabolism)
• RNA Processing, Post-Transcriptional
• RNA, Messenger (metabolism)
• RNA, Ribosomal (metabolism)
• Tandem Mass Spectrometry