Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Jain, M; Mann, TD; Stulić, M; Rao, SP; Kirsch, A; Pullirsch, D; Strobl, X; Rath, C; Reissig, L; Moreth, K; Klein-Rodewald, T; Bekeredjian, R; Gailus-Durner, V; Fuchs, H; Hrabě de Angelis, M; Pablik, E; Cimatti, L; Martin, D; Zinnanti, J; Graier, WF; Sibilia, M; Frank, S; Levanon, EY; Jantsch, MF.
RNA editing of Filamin A pre-mRNA regulates vascular contraction and diastolic blood pressure.
EMBO J. 2018; [OPEN ACCESS]
PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Frank Saša
Graier Wolfgang
Kirsch Andrijana
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Number of Figures: 13
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Abstract:
Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

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