Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth.
Hossein GhanbarianNicole WagnerBeatrice PoloDelphine BaudouyJafar KianiJean-François MichielsFrançois CuzinMinoo RassoulzadeganKay-Dietrich WagnerPublished in: PloS one (2016)
Dnmt2/Trdmt1 is a methyltransferase, which has been shown to methylate tRNAs. Deficient mutants were reported to exhibit various, seemingly unrelated, defects in development and RNA-mediated epigenetic heredity. Here we report a role in a distinct developmental regulation effected by a noncoding RNA. We show that Dnmt2-deficiency in mice results in cardiac hypertrophy. Echocardiographic measurements revealed that cardiac function is preserved notwithstanding the increased dimensions of the organ due to cardiomyocyte enlargement. Mechanistically, activation of the P-TEFb complex, a critical step for cardiac growth, results from increased dissociation of the negatively regulating Rn7sk non-coding RNA component in Dnmt2-deficient cells. Our data suggest that Dnmt2 plays an unexpected role for regulation of cardiac growth by modulating activity of the P-TEFb complex.
Keyphrases
- dna methylation
- left ventricular
- gene expression
- induced apoptosis
- transcription factor
- type diabetes
- mitral valve
- pulmonary hypertension
- angiotensin ii
- cell death
- metabolic syndrome
- nucleic acid
- electronic health record
- replacement therapy
- high fat diet induced
- oxidative stress
- skeletal muscle
- atrial fibrillation
- data analysis
- high glucose