PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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 PMC
Open Access Hybrid
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.
Impact Factor
Scopus SNIP
Scopus
Cited By
Altmetric
10.557
1.622
57
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Adenosine Deaminases Acting On Rna (adar) ; Cardiovascular Disease ; Filamin A (flna) ; Hypertension ; Rna Editing
Language
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Journal EMBO Journal, The
Quellenangaben Volume: , Issue: , Pages: , Article Number: e94813 Supplement: ,
Publisher Wiley
Publishing Place Heidelberg, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Pathology (PATH)
POF-Topic(s) 30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Genetics and Epidemiology
Enabling and Novel Technologies
PSP Element(s) G-500600-001
G-500300-001
G-500692-001
DOI 10.15252/embj.201694813
Scopus ID 85052449831
PubMed ID 30087110
Erfassungsdatum 2018-09-05
[➜Report correction]