This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 813716.
The long non-coding RNA NRON promotes the development of cardiac hypertrophyin the murine heart
Physiological and pathological cardiovascular processes are tightly regulated by several cellular mechanisms. Non-coding RNAs, including long non-coding RNAs (lncRNAs), represent one important class of molecules involved in regulatory processes within the cell. The lncRNA Non-coding repressor of NFAT (NRON) was described as a repressor of nuclear factor of activated T cells (NFAT) in different in vitro studies. Although the calcineurin/NFAT-signaling pathway is one of the most important pathways in pathological cardiac hypertrophy, a potential regulation of hypertrophy by NRON in vivo has remained unclear. Applying subcellular fractionation and RNA-FISH, we found that, unlike what is known from T cells, in cardiomyocytes NRON predominantly localizes to the nucleus. Hypertrophic stimulation in neonatal mouse cardiomyocytes led to a downregulation of NRON, while NRON overexpression led to an increased in expression of hypertrophic markers. To functionally investigate NRON in vivo, they used a mouse model of transverse aortic constriction (TAC)-induced hypertrophy and performed NRON gain- and loss-of-function experiments.
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Citation: Hoepfner J, Leonardy J, Lu D, Schmidt K, Hunkler HJ, Biß S, Foinquinos A, Xiao K, Regalla K, Ramanujam D, Engelhardt S, Bär C, Thum T. The long non-coding RNA NRON promotes the development of cardiac hypertrophy in the murine heart. Mol Ther. 2021 Nov 29:S1525-0016(21)00635-3. doi: 10.1016/j.ymthe.2021.11.018. Epub ahead of print. PMID: 34856383.
Wed, 15 December