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Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation

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Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. / Stellos, Konstantinos; Gatsiou, Aikaterini; Stamatelopoulos, Kimon et al.
In: Nature Medicine, Vol. 22, No. 10, 31.10.2016, p. 1140-1150.

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

Harvard

Stellos, K, Gatsiou, A, Stamatelopoulos, K, Perisic Matic, L, John, D, Lunella, FF, Jaé, N, Rossbach, O, Amrhein, C, Sigala, F, Boon, RA, Fürtig, B, Manavski, Y, You, X, Uchida, S, Keller, T, Boeckel, J-N, Franco-Cereceda, A, Maegdefessel, L, Chen, W, Schwalbe, H, Bindereif, A, Eriksson, P, Hedin, U, Zeiher, AM & Dimmeler, S 2016, 'Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation', Nature Medicine, vol. 22, no. 10, pp. 1140-1150. https://doi.org/10.1038/nm.4172

APA

Stellos, K., Gatsiou, A., Stamatelopoulos, K., Perisic Matic, L., John, D., Lunella, F. F., Jaé, N., Rossbach, O., Amrhein, C., Sigala, F., Boon, R. A., Fürtig, B., Manavski, Y., You, X., Uchida, S., Keller, T., Boeckel, J.-N., Franco-Cereceda, A., Maegdefessel, L., ... Dimmeler, S. (2016). Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nature Medicine, 22(10), 1140-1150. https://doi.org/10.1038/nm.4172

Vancouver

Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF et al. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nature Medicine. 2016 Oct 31;22(10):1140-1150. Epub 2016 Sept 5. doi: 10.1038/nm.4172

Author

Stellos, Konstantinos ; Gatsiou, Aikaterini ; Stamatelopoulos, Kimon et al. / Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. In: Nature Medicine. 2016 ; Vol. 22, No. 10. pp. 1140-1150.

Bibtex

@article{a089ad048d944080b71e212555b7dc7a,
title = "Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation",
abstract = "Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease is unknown. Here we show that cathepsin S mRNA (CTSS), which encodes a cysteine protease associated with angiogenesis and atherosclerosis, is highly edited in human endothelial cells. The 3' untranslated region (3' UTR) of the CTSS transcript contains two inverted repeats, the AluJo and AluSx+ regions, which form a long stem-loop structure that is recognized by ADAR1 as a substrate for editing. RNA editing enables the recruitment of the stabilizing RNA-binding protein human antigen R (HuR; encoded by ELAVL1) to the 3' UTR of the CTSS transcript, thereby controlling CTSS mRNA stability and expression. In endothelial cells, ADAR1 overexpression or treatment of cells with hypoxia or with the inflammatory cytokines interferon-γ and tumor-necrosis-factor-α induces CTSS RNA editing and consequently increases cathepsin S expression. ADAR1 levels and the extent of CTSS RNA editing are associated with changes in cathepsin S levels in patients with atherosclerotic vascular diseases, including subclinical atherosclerosis, coronary artery disease, aortic aneurysms and advanced carotid atherosclerotic disease. These results reveal a previously unrecognized role of RNA editing in gene expression in human atherosclerotic vascular diseases.",
keywords = "3' Untranslated Regions, Adenosine/metabolism, Adenosine Deaminase/genetics, Adult, Aged, Aged, 80 and over, Aortic Aneurysm/genetics, Atherosclerosis/genetics, Carotid Artery Diseases/genetics, Cathepsins/genetics, Coronary Artery Disease/genetics, ELAV-Like Protein 1/genetics, Female, Fluorescent Antibody Technique, Gene Expression Regulation, Gene Knock-In Techniques, Gene Knockdown Techniques, High-Throughput Nucleotide Sequencing, Human Umbilical Vein Endothelial Cells, Humans, Hypoxia/genetics, Immunoblotting, Inosine/metabolism, Interferon-gamma/pharmacology, Male, Middle Aged, RNA Editing/drug effects, RNA Processing, Post-Transcriptional/drug effects, RNA, Messenger/metabolism, RNA-Binding Proteins/genetics, Real-Time Polymerase Chain Reaction, Sequence Analysis, RNA, Tumor Necrosis Factor-alpha/pharmacology",
author = "Konstantinos Stellos and Aikaterini Gatsiou and Kimon Stamatelopoulos and {Perisic Matic}, Ljubica and David John and Lunella, {Federica Francesca} and Nicolas Ja{\'e} and Oliver Rossbach and Carolin Amrhein and Frangiska Sigala and Boon, {Reinier A} and Boris F{\"u}rtig and Yosif Manavski and Xintian You and Shizuka Uchida and Till Keller and Jes-Niels Boeckel and Anders Franco-Cereceda and Lars Maegdefessel and Wei Chen and Harald Schwalbe and Albrecht Bindereif and Per Eriksson and Ulf Hedin and Zeiher, {Andreas M} and Stefanie Dimmeler",
year = "2016",
month = oct,
day = "31",
doi = "10.1038/nm.4172",
language = "English",
volume = "22",
pages = "1140--1150",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation

AU - Stellos, Konstantinos

AU - Gatsiou, Aikaterini

AU - Stamatelopoulos, Kimon

AU - Perisic Matic, Ljubica

AU - John, David

AU - Lunella, Federica Francesca

AU - Jaé, Nicolas

AU - Rossbach, Oliver

AU - Amrhein, Carolin

AU - Sigala, Frangiska

AU - Boon, Reinier A

AU - Fürtig, Boris

AU - Manavski, Yosif

AU - You, Xintian

AU - Uchida, Shizuka

AU - Keller, Till

AU - Boeckel, Jes-Niels

AU - Franco-Cereceda, Anders

AU - Maegdefessel, Lars

AU - Chen, Wei

AU - Schwalbe, Harald

AU - Bindereif, Albrecht

AU - Eriksson, Per

AU - Hedin, Ulf

AU - Zeiher, Andreas M

AU - Dimmeler, Stefanie

PY - 2016/10/31

Y1 - 2016/10/31

N2 - Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease is unknown. Here we show that cathepsin S mRNA (CTSS), which encodes a cysteine protease associated with angiogenesis and atherosclerosis, is highly edited in human endothelial cells. The 3' untranslated region (3' UTR) of the CTSS transcript contains two inverted repeats, the AluJo and AluSx+ regions, which form a long stem-loop structure that is recognized by ADAR1 as a substrate for editing. RNA editing enables the recruitment of the stabilizing RNA-binding protein human antigen R (HuR; encoded by ELAVL1) to the 3' UTR of the CTSS transcript, thereby controlling CTSS mRNA stability and expression. In endothelial cells, ADAR1 overexpression or treatment of cells with hypoxia or with the inflammatory cytokines interferon-γ and tumor-necrosis-factor-α induces CTSS RNA editing and consequently increases cathepsin S expression. ADAR1 levels and the extent of CTSS RNA editing are associated with changes in cathepsin S levels in patients with atherosclerotic vascular diseases, including subclinical atherosclerosis, coronary artery disease, aortic aneurysms and advanced carotid atherosclerotic disease. These results reveal a previously unrecognized role of RNA editing in gene expression in human atherosclerotic vascular diseases.

AB - Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease is unknown. Here we show that cathepsin S mRNA (CTSS), which encodes a cysteine protease associated with angiogenesis and atherosclerosis, is highly edited in human endothelial cells. The 3' untranslated region (3' UTR) of the CTSS transcript contains two inverted repeats, the AluJo and AluSx+ regions, which form a long stem-loop structure that is recognized by ADAR1 as a substrate for editing. RNA editing enables the recruitment of the stabilizing RNA-binding protein human antigen R (HuR; encoded by ELAVL1) to the 3' UTR of the CTSS transcript, thereby controlling CTSS mRNA stability and expression. In endothelial cells, ADAR1 overexpression or treatment of cells with hypoxia or with the inflammatory cytokines interferon-γ and tumor-necrosis-factor-α induces CTSS RNA editing and consequently increases cathepsin S expression. ADAR1 levels and the extent of CTSS RNA editing are associated with changes in cathepsin S levels in patients with atherosclerotic vascular diseases, including subclinical atherosclerosis, coronary artery disease, aortic aneurysms and advanced carotid atherosclerotic disease. These results reveal a previously unrecognized role of RNA editing in gene expression in human atherosclerotic vascular diseases.

KW - 3' Untranslated Regions

KW - Adenosine/metabolism

KW - Adenosine Deaminase/genetics

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Aortic Aneurysm/genetics

KW - Atherosclerosis/genetics

KW - Carotid Artery Diseases/genetics

KW - Cathepsins/genetics

KW - Coronary Artery Disease/genetics

KW - ELAV-Like Protein 1/genetics

KW - Female

KW - Fluorescent Antibody Technique

KW - Gene Expression Regulation

KW - Gene Knock-In Techniques

KW - Gene Knockdown Techniques

KW - High-Throughput Nucleotide Sequencing

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Hypoxia/genetics

KW - Immunoblotting

KW - Inosine/metabolism

KW - Interferon-gamma/pharmacology

KW - Male

KW - Middle Aged

KW - RNA Editing/drug effects

KW - RNA Processing, Post-Transcriptional/drug effects

KW - RNA, Messenger/metabolism

KW - RNA-Binding Proteins/genetics

KW - Real-Time Polymerase Chain Reaction

KW - Sequence Analysis, RNA

KW - Tumor Necrosis Factor-alpha/pharmacology

U2 - 10.1038/nm.4172

DO - 10.1038/nm.4172

M3 - Journal article

C2 - 27595325

VL - 22

SP - 1140

EP - 1150

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 10

ER -