PuSH - Publication Server of Helmholtz Zentrum München: Reduction of A-to-I RNA editing in the failing human heart regulates formation of circular RNAs.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Kokot, K.E.* ; Kneuer, J.M.* ; John, D. * ; Rebs, S.* ; Möbius-Winkler, M.N.* ; Erbe, S.* ; Müller, M.* ; Andritschke, M.* ; Gaul, S.* ; Sheikh, B. ; Haas, J.* ; Thiele, H.* ; Müller, O.J.* ; Hille, S.* ; Leuschner, F.* ; Dimmeler, S.* ; Streckfuss-Bömeke, K.* ; Meder, B.* ; Laufs, U.* ; Boeckel, J.N.*

Reduction of A-to-I RNA editing in the failing human heart regulates formation of circular RNAs.

Basic Res. Cardiol. 117:32 (2022)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Hybrid

Abstract
Metrics
Extra information

Alterations of RNA editing that affect the secondary structure of RNAs can cause human diseases. We therefore studied RNA editing in failing human hearts. Transcriptome sequencing showed that adenosine-to-inosine (A-to-I) RNA editing was responsible for 80% of the editing events in the myocardium. Failing human hearts were characterized by reduced RNA editing. This was primarily attributable to Alu elements in introns of protein-coding genes. In the failing left ventricle, 166 circRNAs were upregulated and 7 circRNAs were downregulated compared to non-failing controls. Most of the upregulated circRNAs were associated with reduced RNA editing in the host gene. ADAR2, which binds to RNA regions that are edited from A-to-I, was decreased in failing human hearts. In vitro, reduction of ADAR2 increased circRNA levels suggesting a causal effect of reduced ADAR2 levels on increased circRNAs in the failing human heart. To gain mechanistic insight, one of the identified upregulated circRNAs with a high reduction of editing in heart failure, AKAP13, was further characterized. ADAR2 reduced the formation of double-stranded structures in AKAP13 pre-mRNA, thereby reducing the stability of Alu elements and the circularization of the resulting circRNA. Overexpression of circAKAP13 impaired the sarcomere regularity of human induced pluripotent stem cell-derived cardiomyocytes. These data show that ADAR2 mediates A-to-I RNA editing in the human heart. A-to-I RNA editing represses the formation of dsRNA structures of Alu elements favoring canonical linear mRNA splicing and inhibiting the formation of circRNAs. The findings are relevant to diseases with reduced RNA editing and increased circRNA levels and provide insights into the human-specific regulation of circRNA formation.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

12.416

0.000