Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth.
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.
Biotechnology Department, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hossein
H
Ghanbarian
Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France.|Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100, Nice, France.
Nicole
N
Wagner
Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100, Nice, France.
Beatrice
B
Polo
Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France.|Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100, Nice, France.
Delphine
D
Baudouy
Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Jafar
J
Kiani
Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France.|Department of Pathology, CHU Nice, Nice, France.
Jean-François
JF
Michiels
Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100, Nice, France.
François
F
Cuzin
Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100, Nice, France.
Minoo
M
Rassoulzadegan
Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France.|Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100, Nice, France.
Kay-Dietrich
http://orcid.org/0000-0001-5483-7760
KD
Wagner
D000818:Animals; D002478:Cells, Cultured; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038081:Organogenesis / Q000235:genetics*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics
D015534:Trans-Activators; C491786:Dnmt2 protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II