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Jain, M.* ; Mann, T.D.* ; Stulić, M.* ; Rao, S.P.* ; 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, W.F.* ; Sibilia, M.* ; Frank, S.* ; Levanon, E.Y.* ; Jantsch, M.F.*

RNA editing of Filamin A pre-mRNA regulates vascular contraction and diastolic blood pressure.

EMBO J.:e94813 (2018)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adenosine Deaminases Acting On Rna (adar) ; Cardiovascular Disease ; Filamin A (flna) ; Hypertension ; Rna Editing
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Quellenangaben Volume: , Issue: , Pages: , Article Number: e94813 Supplement: ,
Publisher Wiley
Publishing Place Heidelberg, Germany
Reviewing status Peer reviewed