Müller, Marion

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Kokot, Karoline E."],["dc.contributor.author","Kneuer, Jasmin M."],["dc.contributor.author","John, David"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Möbius-Winkler, Maximilian N."],["dc.contributor.author","Erbe, Stephan"],["dc.contributor.author","Müller, Marion"],["dc.contributor.author","Andritschke, Michael"],["dc.contributor.author","Gaul, Susanne"],["dc.contributor.author","Sheikh, Bilal N."],["dc.contributor.author","Boeckel, Jes-Niels"],["dc.date.accessioned","2022-07-01T07:35:35Z"],["dc.date.available","2022-07-01T07:35:35Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract 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."],["dc.description.sponsorship"," Deutsche Gesellschaft für Kardiologie-Herz und Kreislaufforschung. http://dx.doi.org/10.13039/501100010578"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Universität Leipzig 501100008678"],["dc.identifier.doi","10.1007/s00395-022-00940-9"],["dc.identifier.pii","940"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112209"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","1435-1803"],["dc.relation.issn","0300-8428"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Reduction of A-to-I RNA editing in the failing human heart regulates formation of circular RNAs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","129"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Genomics, Proteomics & Bioinformatics"],["dc.bibliographiccitation.lastpage","146"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Boeckel, Jes-Niels"],["dc.contributor.author","Möbius-Winkler, Maximilian"],["dc.contributor.author","Müller, Marion"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Eger, Nicole"],["dc.contributor.author","Schoppe, Laura"],["dc.contributor.author","Tappu, Rewati"],["dc.contributor.author","Kokot, Karoline E."],["dc.contributor.author","Kneuer, Jasmin M."],["dc.contributor.author","Gaul, Susanne"],["dc.contributor.author","Meder, Benjamin"],["dc.date.accessioned","2022-12-01T08:30:36Z"],["dc.date.available","2022-12-01T08:30:36Z"],["dc.date.issued","2022"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100003042 Else Kroner-Fresenius-Stiftung"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100004937 BMBF Berlin"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100005970 Deutsche Stiftung für Herzforschung"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100007316 Klaus Tschira Foundation"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100013811 University of Leipzig Faculty of Medicine"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/100010447 DZHK"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/100011272 European Commission Seventh Framework Programme for Research and Technological Development Health"],["dc.identifier.doi","10.1016/j.gpb.2021.01.006"],["dc.identifier.pii","S1672022921001467"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117929"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.issn","1672-0229"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]