학술논문
Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth.
Document Type
Article
Author
Source
Subject
*HEART development
*RNA polymerase II
*METHYLTRANSFERASES
*EPIGENETICS
*NON-coding RNA
*ECHOCARDIOGRAPHY
*CARDIAC hypertrophy
*GENETICS
*DIAGNOSIS
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Language
ISSN
1932-6203
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. [ABSTRACT FROM AUTHOR]