Journal
PLOS ONE
Volume 11, Issue 6, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0156953
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Funding
- French Government (National Research Agency, ANR) through the Investments for the Future LABEX SIGNALIFE program [ANR-11-LABX-0028-01]
- Association pour la Recherche sur le Cancer
- Fondation de France
- Ligue Nationale Contre le Cancer
- Agence Nationale de la Recherche France [ANR-08-GENOPAT-011 Epipath-Parapath]
- Shahid Beheshti University of Medical Sciences, Iran
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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.
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