PXD024974-1

PXD024974 is an original dataset announced via ProteomeXchange.

Title	Irf7 orchestrates the immunological reaction in cardiomyocytes upon Adar1 deletion
Description	Adenosine deaminases acting on RNA (Adar1 and Adar2) catalyze I-to-A RNA editing, a post-transcriptional mechanism involved in multiple cellular functions. The role of Adar1-dependent RNA editing in cardiomyocytes (CMs) remains unclear. Here we show that conditional deletion of Adar1 in CMs results in myocarditis progressively evolving into dilated cardiomyopathy and heart failure at only 6 months of age. Adar1 depletion drives activation of interferon signaling genes (ISGs) in the absence of apoptosis and cytokine activation, and reduces the hypertrophic response of CMs upon pressure overload. Interestingly, ablation of the cytosolic sensor MDA5 prevents cardiac ISG activation and delays disease onset, but does not rescue the long-term lethal phenotype elicited by conditional deletion of Adar1. Retention of a single catalytically inactive Adar1 allele in CMs, in combination with MDA5 depletion, however, completely restores the cardiac function and prevents heart failure. Finally, ablation of interferon regulatory factor 7 (Irf7) attenuates the phenotype of Adar1-deficient CMs to a similar extent as MDA5 depletion, highlighting Irf7 as the main regulator of the immune response triggered by lack of Adar1 in CMs.
HostingRepository	PRIDE
AnnounceDate	2022-08-25
AnnouncementXML	Submission_2022-08-25_04:47:05.663.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Graumann
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-24 09:24:11	ID requested
⏵ 1	2022-08-25 04:47:06	announced
2	2023-11-14 08:52:40	announced	2023-11-14: Updated project metadata.

10.1161/CIRCRESAHA.122.320839;

submitter keyword: RNA editing, ADAR1, cardiomyocytes, immune response, dilated cardiomyopathy, myocarditis, IRF7

Thomas Braum
contact affiliation	Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
contact email	thomas.braun@mpi-bn.mpg.de
lab head
Johannes Graumann
contact affiliation	Max Planck Institute for Heart and Lung Research
contact email	johannes.graumann@uni-marburg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/08/PXD024974

PRIDE project URI

• PRIDE
  1. PXD024974
     1. Label: PRIDE project
     2. Name: Irf7 orchestrates the immunological reaction in cardiomyocytes upon Adar1 deletion