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Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. / Vlachogiannis, Nikolaos I; Sachse, Marco; Georgiopoulos, Georgios et al.
In: Journal of molecular and cellular cardiology, Vol. 160, 30.11.2021, p. 111-120.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Vlachogiannis, NI, Sachse, M, Georgiopoulos, G, Zormpas, E, Bampatsias, D, Delialis, D, Bonini, F, Galyfos, G, Sigala, F, Stamatelopoulos, K, Gatsiou, A & Stellos, K 2021, 'Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease', Journal of molecular and cellular cardiology, vol. 160, pp. 111-120. https://doi.org/10.1016/j.yjmcc.2021.07.005

APA

Vlachogiannis, N. I., Sachse, M., Georgiopoulos, G., Zormpas, E., Bampatsias, D., Delialis, D., Bonini, F., Galyfos, G., Sigala, F., Stamatelopoulos, K., Gatsiou, A., & Stellos, K. (2021). Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. Journal of molecular and cellular cardiology, 160, 111-120. https://doi.org/10.1016/j.yjmcc.2021.07.005

Vancouver

Vlachogiannis NI, Sachse M, Georgiopoulos G, Zormpas E, Bampatsias D, Delialis D et al. Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. Journal of molecular and cellular cardiology. 2021 Nov 30;160:111-120. Epub 2021 Jul 27. doi: 10.1016/j.yjmcc.2021.07.005

Author

Vlachogiannis, Nikolaos I ; Sachse, Marco ; Georgiopoulos, Georgios et al. / Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. In: Journal of molecular and cellular cardiology. 2021 ; Vol. 160. pp. 111-120.

Bibtex

@article{32694a8d093a4dc4af1de98e9727f4fb,
title = "Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease",
abstract = "Long non-coding RNAs (lncRNAs) have emerged as critical regulators in human disease including atherosclerosis. However, the mechanisms involved in the post-transcriptional regulation of the expression of disease-associated lncRNAs are not fully understood. Gene expression studies revealed that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) lncRNA expression was increased by >2-fold in peripheral blood mononuclear cells (PBMCs) derived from patients with coronary artery disease (CAD) or in carotid artery atherosclerotic plaques. We observed a linear association between NEAT1 lncRNA expression and prevalence of CAD which was independent of age, sex, cardiovascular traditional risk factors and renal function. NEAT1 expression was induced by TNF-α, while silencing of NEAT1 profoundly attenuated the TNF-α-induced vascular endothelial cell pro-inflammatory response as defined by the expression of CXCL8, CCL2, VCAM1 and ICAM1. Overexpression of the RNA editing enzyme adenosine deaminase acting on RNA-1 (ADAR1), but not of its editing-deficient mutant, upregulated NEAT1 levels. Conversely, silencing of ADAR1 suppressed the basal levels and the TNF-α-induced increase of NEAT1. NEAT1 lncRNA expression was strongly associated with ADAR1 in CAD and peripheral arterial vascular disease. RNA editing mapping studies revealed the presence of several inosines in close proximity to AU-rich elements within the AluSx3+/AluJo- double-stranded RNA complex. Silencing of the stabilizing RNA-binding protein AUF1 reduced NEAT1 levels while silencing of ADAR1 profoundly affected the binding capacity of AUF1 to NEAT1. Together, our findings propose a mechanism by which ADAR1-catalyzed A-to-I RNA editing controls NEAT1 lncRNA stability in ASCVD.",
keywords = "Adenosine/metabolism, Adenosine Deaminase/genetics, Adult, Aged, Aged, 80 and over, Alu Elements/genetics, Atherosclerosis/blood, Binding Sites, Cells, Cultured, Cohort Studies, Coronary Artery Disease/blood, Female, Gene Silencing, Heterogeneous Nuclear Ribonucleoprotein D0/genetics, Human Umbilical Vein Endothelial Cells, Humans, Inosine/metabolism, Leukocytes, Mononuclear/metabolism, Male, Middle Aged, Plaque, Atherosclerotic/blood, RNA Editing/genetics, RNA Stability/genetics, RNA, Long Noncoding/genetics, RNA-Binding Proteins/genetics, Signal Transduction/genetics, Transfection",
author = "Vlachogiannis, {Nikolaos I} and Marco Sachse and Georgios Georgiopoulos and Eleftherios Zormpas and Dimitrios Bampatsias and Dimitrios Delialis and Francesca Bonini and George Galyfos and Fragiska Sigala and Kimon Stamatelopoulos and Aikaterini Gatsiou and Konstantinos Stellos",
note = "Copyright {\textcopyright} 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.",
year = "2021",
month = nov,
day = "30",
doi = "10.1016/j.yjmcc.2021.07.005",
language = "English",
volume = "160",
pages = "111--120",
journal = "Journal of molecular and cellular cardiology",
issn = "0022-2828",
publisher = "Academic Press",

}

RIS

TY - JOUR

T1 - Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease

AU - Vlachogiannis, Nikolaos I

AU - Sachse, Marco

AU - Georgiopoulos, Georgios

AU - Zormpas, Eleftherios

AU - Bampatsias, Dimitrios

AU - Delialis, Dimitrios

AU - Bonini, Francesca

AU - Galyfos, George

AU - Sigala, Fragiska

AU - Stamatelopoulos, Kimon

AU - Gatsiou, Aikaterini

AU - Stellos, Konstantinos

N1 - Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2021/11/30

Y1 - 2021/11/30

N2 - Long non-coding RNAs (lncRNAs) have emerged as critical regulators in human disease including atherosclerosis. However, the mechanisms involved in the post-transcriptional regulation of the expression of disease-associated lncRNAs are not fully understood. Gene expression studies revealed that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) lncRNA expression was increased by >2-fold in peripheral blood mononuclear cells (PBMCs) derived from patients with coronary artery disease (CAD) or in carotid artery atherosclerotic plaques. We observed a linear association between NEAT1 lncRNA expression and prevalence of CAD which was independent of age, sex, cardiovascular traditional risk factors and renal function. NEAT1 expression was induced by TNF-α, while silencing of NEAT1 profoundly attenuated the TNF-α-induced vascular endothelial cell pro-inflammatory response as defined by the expression of CXCL8, CCL2, VCAM1 and ICAM1. Overexpression of the RNA editing enzyme adenosine deaminase acting on RNA-1 (ADAR1), but not of its editing-deficient mutant, upregulated NEAT1 levels. Conversely, silencing of ADAR1 suppressed the basal levels and the TNF-α-induced increase of NEAT1. NEAT1 lncRNA expression was strongly associated with ADAR1 in CAD and peripheral arterial vascular disease. RNA editing mapping studies revealed the presence of several inosines in close proximity to AU-rich elements within the AluSx3+/AluJo- double-stranded RNA complex. Silencing of the stabilizing RNA-binding protein AUF1 reduced NEAT1 levels while silencing of ADAR1 profoundly affected the binding capacity of AUF1 to NEAT1. Together, our findings propose a mechanism by which ADAR1-catalyzed A-to-I RNA editing controls NEAT1 lncRNA stability in ASCVD.

AB - Long non-coding RNAs (lncRNAs) have emerged as critical regulators in human disease including atherosclerosis. However, the mechanisms involved in the post-transcriptional regulation of the expression of disease-associated lncRNAs are not fully understood. Gene expression studies revealed that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) lncRNA expression was increased by >2-fold in peripheral blood mononuclear cells (PBMCs) derived from patients with coronary artery disease (CAD) or in carotid artery atherosclerotic plaques. We observed a linear association between NEAT1 lncRNA expression and prevalence of CAD which was independent of age, sex, cardiovascular traditional risk factors and renal function. NEAT1 expression was induced by TNF-α, while silencing of NEAT1 profoundly attenuated the TNF-α-induced vascular endothelial cell pro-inflammatory response as defined by the expression of CXCL8, CCL2, VCAM1 and ICAM1. Overexpression of the RNA editing enzyme adenosine deaminase acting on RNA-1 (ADAR1), but not of its editing-deficient mutant, upregulated NEAT1 levels. Conversely, silencing of ADAR1 suppressed the basal levels and the TNF-α-induced increase of NEAT1. NEAT1 lncRNA expression was strongly associated with ADAR1 in CAD and peripheral arterial vascular disease. RNA editing mapping studies revealed the presence of several inosines in close proximity to AU-rich elements within the AluSx3+/AluJo- double-stranded RNA complex. Silencing of the stabilizing RNA-binding protein AUF1 reduced NEAT1 levels while silencing of ADAR1 profoundly affected the binding capacity of AUF1 to NEAT1. Together, our findings propose a mechanism by which ADAR1-catalyzed A-to-I RNA editing controls NEAT1 lncRNA stability in ASCVD.

KW - Adenosine/metabolism

KW - Adenosine Deaminase/genetics

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alu Elements/genetics

KW - Atherosclerosis/blood

KW - Binding Sites

KW - Cells, Cultured

KW - Cohort Studies

KW - Coronary Artery Disease/blood

KW - Female

KW - Gene Silencing

KW - Heterogeneous Nuclear Ribonucleoprotein D0/genetics

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Inosine/metabolism

KW - Leukocytes, Mononuclear/metabolism

KW - Male

KW - Middle Aged

KW - Plaque, Atherosclerotic/blood

KW - RNA Editing/genetics

KW - RNA Stability/genetics

KW - RNA, Long Noncoding/genetics

KW - RNA-Binding Proteins/genetics

KW - Signal Transduction/genetics

KW - Transfection

U2 - 10.1016/j.yjmcc.2021.07.005

DO - 10.1016/j.yjmcc.2021.07.005

M3 - Journal article

C2 - 34302813

VL - 160

SP - 111

EP - 120

JO - Journal of molecular and cellular cardiology

JF - Journal of molecular and cellular cardiology

SN - 0022-2828

ER -