Project Details
Projekt
Role of the long intergenic non-coding (linc) RNA NRON in cardiac disease
Subject Area
Cardiology, Angiology
Term
from 2013 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 235253286
The mammalian genome consists of numerous -foci- of transcription that are separated by long stretches of intergenic space, also entitled -the dark matter of the genome- because of our limited understanding. Long non-coding RNAs (lincRNAs) are located and transcribed within these intergenic stretches, and recent evidence suggest some of those sequences to be largely involved in gene regulation. However, the role of lincRNAs in cardiac diseases has never been explored so far. Our preliminary results show that cardiac hypertrophic substances suppress cardiomyocyte expression of the lincRNA NRON (Non-coding Regulator of NFAT). Further, we found NRON expression to be impaired in different cardiac disease models (myocardial infarction and transverse aortic constriction) and NRON silencing in cultured cardiomyocytes resulted in hypertrophy. In the present grant application, we propose to perform an in depth analysis of the role of the lincRNA NRON in cardiac diseases. For this purpose, we will employ animal models with genetic deletion of NRON to study if these animals are more prone to cardiac disease. Next, we will test if adenoviral mediated gene therapy to restore NRON expression has any beneficial effects on cardiac function based on our promising in vitro results. This study will be the first to highlight the role of a lincRNA in cardiac diseases and may open-up opportunities for new therapeutic modalities for cardiac diseases.
DFG Programme
Research Grants
