Journal Article

Increased A-to-I RNA editing in atherosclerosis and cardiomyopathies

Kopel, Eli, Levanon, Erez Y., Eisenberg, Eli, Mann, Tomer D.

2023

Overview

Adenosine-to-inosine RNA editing is essential to prevent undesired immune activation. This diverse process alters the genetic content of the RNA and may recode proteins, change splice sites and miRNA targets, and mimic genomic mutations. Recent studies have associated or implicated aberrant editing with pathological conditions, including cancer, autoimmune diseases, and neurological and psychiatric conditions. RNA editing patterns in cardiovascular tissues have not been investigated systematically so far, and little is known about its potential role in cardiac diseases. Some hints suggest robust editing in this system, including the fact that ADARB1 (ADAR2), the main coding-sequence editor, is most highly expressed in these tissues. Here we characterized RNA editing in the heart and arteries and examined a contributory role to the development of atherosclerosis and two structural heart diseases -Ischemic and Dilated Cardiomyopathies. Analyzing hundreds of RNA-seq samples taken from the heart and arteries of cardiac patients and controls, we find that global editing, alongside inflammatory gene expression, is increased in patients with atherosclerosis, cardiomyopathies, and heart failure. We describe a single recoding editing site and suggest it as a target for focused research. This recoding editing site in the IGFBP7 gene is one of the only evolutionary conserved sites between mammals, and we found it exhibits consistently increased levels of editing in these patients. Our findings reveal that RNA editing is abundant in arteries and is elevated in several key cardiovascular conditions. They thus provide a roadmap for basic and translational research of RNA as a mediator of atherosclerosis and non-genetic cardiomyopathies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenosine / Animals / Arteries / Arteriosclerosis / Atherosclerosis / Atherosclerosis - genetics / Autoimmune diseases / Biology and Life Sciences / Cardiac patients / Cardiomyopathies - genetics / Cardiomyopathy / Cardiovascular disease / Cardiovascular diseases / Coding / Congestive heart failure / Coronary artery disease / Coronary vessels / Development and progression / Editing / Evolutionary conservation / Gene expression / Genes / Genetic aspects / Genomes / Heart / Heart diseases / Heart failure / Humans / Immune response / Immune system / Inflammation / Interferon / Ischemia / Mammals - genetics / Medical research / Medicine and Health Sciences / Medicine, Experimental / Methods / miRNA / Neoplasms / Patients / Proteins / Quality control / Ribonucleic acid / RNA / RNA editing / RNA Editing - genetics / RNA processing / Vein & artery diseases