Abstract
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.
Highlights
Dnmt2/Trdmt1 is a member of the cytosine-5 methyltransferase family and shows strong sequence conservation to the catalytic motifs of established DNA methyltransferases [1]
We have shown previously that transcriptional induction of Cdk9 following small non-coding RNAs injection into one-cell embryos results in cardiac hypertrophy in mice [20]
To investigate a potential role of Dnmt2 for cardiac growth, we examined Cdk9, RNA pol II phosphorylation, and Rn7sk in Dnmt2-deficient mice compared to wild-type littermates
Summary
Dnmt2/Trdmt is a member of the cytosine-5 methyltransferase family and shows strong sequence conservation to the catalytic motifs of established DNA methyltransferases [1]. In Zebrafish, Dnmt knockdown experiments have been shown to induce lethal differentiation defects in the retina, liver, and brain [4]. Phalke et al have indicated that Dnmt controls transposable elements in Drosophila [5] and Drosophila mutants showed reduced viability under stress conditions [3]. Dnmt plays a role in non-random sister chromatid segregation in adult testicular stem cells in Drosophila [6]. Recent studies in mice have shown that RNA- mediated epigenetic heredity requires Dnmt2 [7] and that endochondral
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
